Flexible manufacturing system

ABSTRACT

A flexible, multi-product, multi-technology, expandable facility for manufacturing products, such as biologicals, pharmaceuticals, or chemicals, and manufacturing processes using elements of such a facility.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is the U.S. national phase of International Patent Application No.PCT/US2009/069204, filed Dec. 22, 2009, and which claims priority toU.S. Provisional Patent Application No. 61/140,339, filed Dec. 23, 2008,and U.S. Provisional Patent Application No. 61/227,658, filed Jul. 22,2009, the entire contents of each of which are hereby incorporatedherein by reference.

FIELD OF THE INVENTION

The invention relates to a flexible, multi-product, multi-technology,expandable facility for manufacturing products, such as biologicals,pharmaceuticals or chemicals, and manufacturing processes using elementsof such a facility.

BACKGROUND

Conventional manufacturing facilities for the production of biologicals,pharmaceuticals and chemicals (e.g., drugs) are typically designed for aspecific type of product and utilize fixed production components andsystems. Generally, different types of technologies or products, e.g.mammalian cell production of proteins, versus mammalian cell propagationof viruses, versus bacterial protein production, require construction ofentirely different manufacturing facilities or manufacturing suiteswithin a manufacturing facility. Significant amounts of time generallyare required to construct, reconfigure or upgrade a manufacturingfacility, as well as to complete a changeover process (e.g., cleaning)between manufacturing campaigns of similar or different products. Somemanufacturing facilities may house multiple manufacturing suites toallow parallel manufacturing campaigns, but limitations remain in thisconfiguration, such as for example, the time required to convert ormodify a particular manufacturing suite for use in manufacturing adifferent product (e.g., different technologies or types of products),as well as to complete a changeover process (e.g., cleaning) betweenmanufacturing campaigns of similar or different products. In addition,the potential for cross-contamination between different types oftechnology or products may limit the ability to house parallelproduction systems within the same facility.

SUMMARY OF THE DISCLOSURE

The invention provides a manufacturing system comprising (a) a core thatis adapted to supply utilities for multiple manufacturing processes andpreferably is capable of high capacity supply, (b) and at least two,three, four, five, six, seven, eight, nine, ten or more movablemanufacturing bays adapted to be removably coupled to the core andadapted for receiving the utilities supplied from the core. In someembodiments, within the workspace defined by each bay, there is afacility for performing one or more manufacturing processes, or portionsor steps of manufacturing processes, which can optionally be performedin parallel. The facility may comprise a plurality of components, eachof which performs one or more portions or steps of a chemical, abiological, a pharmaceutical, or some other manufacturing process. Themanufacturing system optionally includes a plurality of clean connectareas positioned adjacent to the manufacturing bays when connected tothe core for controlling access to the manufacturing bays and/orproviding a clean area for making the utility connections between thecore and the manufacturing bays. The manufacturing system furtheroptionally includes a plurality of upper docking collars positionedabove the bays when connected to the core for supplying one or moreutilities to the bays (e.g., under the force of gravity). Themanufacturing system optionally comprises one, two, or more holdingareas where a movable bay can be cleaned, and where optionally theconfiguration of components that perform the manufacturing process, orportions or steps of manufacturing processes, can be reconfigured. Themanufacturing system optionally comprises a drain, adapted to beremovably connected to the one or more movable manufacturing bays, fordischarging waste generated during a manufacturing process. The drainfor discharging waste is preferably isolated from the core, so as toavoid contamination of the core.

The invention also provides methods of manufacturing products thatutilize one or more of the components of such a manufacturing system.The systems and methods of the invention provide a number of benefits,including flexibility and the ability to reduce the time and cost ofreconfiguring manufacturing from one technology and/or product to adifferent technology and/or product (e.g., bacterial host cells,yeast/fungal host cells, insect host cells, mammalian host cellsproducing protein, mammalian host cells producing virus, plant cells oralgae), and/or upgrading to newer, more efficient technology, and/orchanging production capacity (increasing or decreasing production) orbatch size (e.g., 100 L to 2750 L, 5,000 L to 20,000 L or vice versa),and/or decreasing the changeover time from a first batch production runto a second batch production run, which may be of the same or adifferent type of production run as the first production run, and/orchanging from manufacturing suitable for pre-clinical purposes (GLP, orGood Laboratory Practice) to manufacturing suitable for FDA or othergovernment regulatory agency approved therapeutics (GMP, or GoodManufacturing Practice), or vice versa.

In addition, the systems and methods of the invention provide theadvantage of efficiently operating the manufacturing system at fullcapacity with all available manufacturing bays operating. For example,manufacturing processes utilizing different technologies can each beperformed in parallel, and/or GLP and GMP manufacturing can be performedin parallel, and/or small scale (e.g., teaching or pilot scale) andlarge scale manufacturing can be performed in parallel, e.g. byoperating multiple manufacturing bays that have differentconfigurations. The systems and methods offer the additional benefit ofpermitting ready expansion from low production capacity to higherproduction capacity by adding more similar or identical bays. Down timeis minimized, particularly by utilizing the holding area to preparemanufacturing bays, because production can be switched from one productto another almost immediately by disconnecting one bay from the core andreconnecting a second bay to the core. For example, the manufacturingsystem can manufacture one product for a period of time (e.g., 1, 2, 3weeks, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months), and a secondproduct for the next period of time (e.g., 1, 2, 3 weeks, 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11 or 12 months), and a third product for the thirdperiod of time. As one example, the manufacturing system can manufactureone product for one month, and a second product for the next month. Asanother example, the manufacturing system can manufacture one productfor two months, a second product for the next month, and a third productfor the next two months, and so on in any combination of time periodsand products. Alternatively, the first, second and third products can bemanufactured simultaneously. Alternatively or in addition, themanufacturing system may be used for the manufacturing of a batch of afirst product in a first bay, followed by disconnecting the first bayfrom the core and connecting a second bay to the core, wherein thesecond bay may be used for the manufacturing of a batch of the firstproduct or a second product. The second bay then may be disconnectedfrom the core and a third bay or the first bay connected for themanufacturing of a batch of the first product, the second product or athird product. Batch manufacturing may be repeated in this manner forany desired period of time and/or combination of products. Similarly,the same configurations and methods apply where the first, second, thirdor more manufacturing processes referenced herein are portions or stepsof an overall manufacturing process to produce a final product orintermediate product (e.g. where the first product, second product orthird product are intermediate products, or intermediate stages ofmanufacture, produced en route to the final pharmaceutical product). Insuch embodiments, the intermediate products may be readily transferredfrom a first bay to a second bay, e.g. via a transfer panel (e.g.,transfer conduit, transfer junction, transfer cabinet, transfer chamber,etc.) or corridor (e.g., controlled corridor). This ability to switchquickly from one product to another, to manufacture multiple productssimultaneously, or to repeatedly manufacture the same products at afaster rate allows manufacturers to keep up with product demand and alsopermits the novel concept of just-in-tune manufacturing fortherapeutics.

The manufacturing system and methods of the invention offer the addedadvantage of providing secure and controlled employee access to multipledistinct and potentially proprietary technologies. In a singlemanufacturing system, each manufacturing bay can have a separate accessand separate security system, such that different companies could own orotherwise arrange for use of (e.g., lease) different bays and permitonly their authorized employees to access the company's proprietarytechnologies. In some embodiments, the core and at least onemanufacturing bay have different personnel with no cross contact.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of one embodiment of a manufacturing system of theinvention;

FIG. 2 is a side view of the manufacturing system of FIG. 1 including anoptional drain and waste receptacle;

FIG. 3 is a plan view of another embodiment of a manufacturing system ofthe invention;

FIG. 4 is a plan view of another embodiment of a manufacturing system ofthe invention;

FIG. 5 is a plan view of another embodiment of a manufacturing system ofthe invention;

FIG. 6 is a side view of an optional upper docking collar; and

FIG. 7 is a plan view of another embodiment of a manufacturing system ofthe invention.

DETAILED DESCRIPTION

With reference to FIGS. 1 and 2, some embodiments of the manufacturingsystem 10 of the present disclosure comprise a core 12 and a pluralityof movable manufacturing bays 14 disposed within an optional housing 16,as will be described in further detail below. In the embodiment depictedin FIG. 1, the system 10 includes first through sixth movablemanufacturing bays 14 a-14 f. The bays 14 can be constructed ofgenerally any material and are generally box-shaped in the currentlydisclosed embodiment. Other shapes are also intended to be within thescope of the invention. The bays may be of a variety of sizes suitablefor the intended manufacturing use, provided the bays are of sufficientsize and configuration to permit one or more personnel to occupy the bayin order to perform a manufacturing process, or portions or steps ofmanufacturing processes, and provided the bays are of a size that ismovable, such as for example, by one or more means of movement asprovided herein. The term “bay” used throughout the present disclosureis merely an exemplary term, and meant to include generally anyfree-standing structure that is disposed outside of (e.g., separatefrom) the core 12, movable relative to the core 12, and defining anenclosed or partly enclosed space for performing a task or a group oftasks. Preferably, a bay is of appropriate size and configuration forone or more personnel to enter and perform a task or a group of tasks(e.g., manufacturing processes, portion or steps of a manufacturingprocess). As such, persons having ordinary skill in the art wouldunderstand that similar structures can alternatively be referred to asmodules, suites, trailers, mobile units, pods, buildings, etc., orgenerally any other term that can be used to describe a movablestructure defining an enclosed workspace as described herein.

The core 12, which can optionally comprise a “clean core,” supplies twoor more, or three or more utilities, for example, to the manufacturingbays 14, wherein at least two or three of the two or more or three ormore utilities are selected from the group consisting of (a) clean air,(b) clean water, (c) electricity, (d) oxygen, and (e) carbon dioxide. Inan alternative embodiment, the three or more utilities can be selectedfrom the group consisting of (a) air, (b) water, (c) electricity, (d)oxygen, and (e) carbon dioxide. In another alternative embodiment, thethree or more utilities can be selected from the group consisting of (a)clean air, (b) sterile water, (c) electricity, (d) oxygen, and (e)carbon dioxide. In yet another embodiment, the three or more utilitiescan be selected from the group consisting of (a) air, (b) sterile water,(c) electricity, (d) oxygen, and (e) carbon dioxide. The term “core”used throughout the present disclosure includes any free-standingbuilding, portion of a building or other structure disposed entirelyseparate from the bays 14 such that the core 12 can be sealed from thebays 14 and the bays 14 can be sealed from the core 12. Moreover, theposition or location of the “core” relative to the bays 14 is notlimited to any of the positions or locations described herein, butrather, can include any building, portion of a building, or structurepositioned relative to any of the other system components including thebays 14. As such, the term “core” is not limited to being located in thecenter of the system or in any other location. Moreover, as mentionedabove, the bays 14 are disposed outside of the core 12, and therefore,the core 12 does not accommodate, surround, or otherwise contain thebays 14.

“Clean water,” as used herein, can include, for example, filtered water,de-ionized water, sterile water, distilled water, purified water (e.g.,USP purified water, EP purified water), water for injection (e.g., USPWFI, EP WFI), USP sterile water for injection, USP sterile water forinhalation, USP bacteriostatic water for injection, USP sterile waterfor irrigation, or highly purified water (e.g., EP HPW). The USPdesignation means that the water is the subject of an official monographin the current US PHARMACOPEIA with various specifications for eachtype. Similarly, the EP designation means that the water is the subjectof standards of the European Pharmacopoeia for water quality in drugmanufacturing processes.

“Clean air,” as used herein, can be defined by one of two standards usedto test and categorize the class of air. These two standards include theUnited States Federal Standard 209E and the International Standard ISO14644-1. Both standards define teens, identify procedures for collectingand testing the air, and provide the statistical analysis required tointerpret the data. Federal Standard 209E classifications of air includeClass 1, Class 10, Class 100, Class 1,000, Class 10,000, and Class100,000. The class number (e.g., 100) is the maximum allowable number ofparticles 0.5 microns and larger per cubic foot of air; the lower thenumber, the cleaner the air. The ISO classifications are rated as ISOClass 1, ISO Class 2, ISO Class 3, etc. through ISO Class 9. Class 1under both standards indicates the cleanest, ultrapure air. The ISOClass 2 correlates most closely to Federal Standard Class 100.Therefore, in accordance with the present application, “clean air” caninclude, for example, any air classified in the range of classes fromclass 100 to class 100,000 under US Federal Standard 209E and, in oneembodiment, in the range of classes from class 10,000 to class 100,000under US Federal Standard 209E.

Further utilities that can be supplied from the core 12 include, forexample, (a) clean air, (b) atmospheric air, (c) sterile water, (d)non-sterile water; (e) electricity, (f) a liquid coolant; (g) oxygen,(h) carbon dioxide, (i) nitrogen, (j) argon, (k) helium, (l) purifiedwater (e.g., USP PWS, USP WFI), (m) steam, (n) clean air (e.g., filteredair), (o) communications (e.g., telephone, data, local area network),(p) non-potable water, (q) potable (i.e., drinkable) water, (r) tapwater, (s) well water, and (t) a liquid solution useful in amanufacturing process (e.g., a nutritional media, a dilution buffer,and/or a purification media).

In one embodiment, the core 12 can be a stand-alone structure built in afixed location. In other embodiments, the core 12 may be a stand-alonestructure that itself is movable on wheels, rails, tracks, by liftingand placement (e.g., by a crane, a crane on overhead rails, etc.),airlift, hovercraft, or other air cushion, or by other means known inthe art. In some embodiments, at least some of the utilities can bestored within the core 12 itself. For example, utilities in gas orliquid form can be contained within reservoirs, tanks, or othercontainers housed within the core 12, and electricity could foreseeablybe supplied from a generator stored within the core. In someembodiments, the core 12 may require connection to one or more incomingutilities such as water, electricity, one or more gases, a computernetwork line, an internet line, etc.

The core 12 depicted in FIG. 1 includes a hexagonal architecturedefining six (6) distinct dock positions 18 a-18 f. Each dock position18 a-18 f is adapted to be removably coupled to a movable manufacturingbay 14, as depicted. As such, in the disclosed embodiment, the core 12and the movable manufacturing bays 14 are arranged in a hub and spokeconfiguration with the movable manufacturing bays 14 circumferentiallyspaced around the core 12. A linear arrangement is equally suitable, aswill be described below with reference to FIGS. 4, 5, and 7, forexample, and one of ordinary skill in the art can envision a number ofsuitable configurations for the core 12 and manufacturing bays 14. Thatis, the core 12 and bays 14 are not limited to the architecture andconfiguration depicted in the attached FIGS. 1-7, but rather, mayinclude generally any architecture and configuration. For example, thecore 12 may include a square, a rectangular, or an octagonalarchitecture, or generally any other shape capable of serving theintended purpose.

The movable manufacturing bays 14 of FIG. 1 are each removably coupledto the core 12 and receive the utilities. In one embodiment, the bays 14may be removably coupled to the core 12 via one or more threadedcouplings, one or more quick-connect couplings, one or morequick-disconnect couplings, one or more male/female connectors, one ormore sanitary couplings, one or more sanitary fluid connectors, one ormore steam-in-place connectors, one or more air duct connectors, and/orany other foreseeable mechanism capable of serving the intended purpose.In one embodiment, the bays 14 do not actually physically removablyconnect to the core 12 (e.g., direct contact between the exterior of thebays and exterior of the core), but rather, just to the fittings orother devices that deliver the utilities. Such an embodiment includes,for example, bays that are in close proximity (e.g., adjacent) to thecore, or a distance from the core (e.g., a different area within thesame housing) and still falls within the means of being “coupled” to thecore 12, as used herein. In other embodiments, the bays 14 can also befixedly and rigidly connected to the core 12. Such a configuration canadvantageously help control and/or limit the motion of the bays 14relative to the core 12. For example, because the bays 14 are movable,it is foreseeable that they may be equipped with a suspension system,for example, to facilitate their maneuverability. Such suspensionsystems could include springs and/or other dampeners that would enablethe bays 14 to move up and down, and rock side to side, for example, inresponse to loading or movement over uneven terrain. However, somemanufacturing processes and/or components for performing manufacturingprocesses may be sensitive to such movements. Therefore, rigidly fixingthe bays 14 to the core 12 can prevent such movement and ensure properprocess and component performance. In one embodiment, the bays 14 can befixed to the core 12 with fixation devices such as threaded fasteners,tongue and groove mechanisms, cam-locks, manual latch/locking systems,locking/coupling systems, and/or any other coupling devices or fixationdevices. In some embodiments, such fixation devices could be containedwithin a skirt system, for example, to maintain cleanliness. In otherembodiments, the core 12 and/or the bays 14 could foreseeably beequipped with one or more jack-type mechanisms for raising the bays 14off of the floor to prevent motion due to the suspension system. Thisconfiguration may be particularly advantageous when the bays are notfixedly and rigidly connected to the core. The one or more jacks may behydraulic, pneumatic, mechanical, electro-mechanical, or any other knowntype. The jack-type system could be used instead of rigidly fixing thebays 14 to the core 12, or in addition thereto. The jack-type systemscould also be used to level the bays 14. The bays 14 could include otherleveling devices, which could foreseeably include automatic levelingdevices. Moreover, the bays 14 could be equipped with braking mechanismsthat prevent the bays 14 from moving away from the core 12 whenactivated.

Still referring to FIG. 1, each bay 14 defines a workspace 20accommodating a facility 22 for performing a manufacturing process. Aswill be understood from the complete description set forth herein, theterm “facility” is intended to include any and everything that can beaccommodated within the bays 14, but for the actual operating personnel.For example, the term “facility” can include space within the bays 14,whether divided from (e.g., separated by walls or other barriers) orcontinuous with the remainder of the space within the bay 14. Inaddition, the term “facility” can include empty space within the bays 14or one or more pieces of equipment for performing any one or more of theprocesses or portions of processes described herein. Moreover, the term“facility” can include equipment that is generally unrelated toperforming any of the processes or portions of processes describedherein such as ambient lighting equipment, coat hangers, lockers,cabinetry, etc. The workspace 20 is defined as the interior portion ofthe bay 14, within which a manufacturing process or portions or steps ofthe process is/are carried out.

More specifically, the first bay 14 a accommodates a first facility 22 afor performing a first manufacturing process, the second bay 14 baccommodates a second facility 22 b for performing a secondmanufacturing process, and so on. This configuration advantageouslyenables the various facilities 22 to perform multiple overallmanufacturing processes, or portions or steps of the same overallmanufacturing process, in parallel, or in series. For the sake ofclarity, only the first and second movable manufacturing bays 14 a, 14 bare depicted as including facilities 22 a, 22 b, but it should beunderstood that each of the remaining bays 14 c-14 f also includerespective facilities. The workspace 20 of each bay 14 is isolated fromthe workspaces 20 of the other bays 14. The workspaces are preferablyisolated so as to avoid contaminating the respective manufacturingprocesses with raw materials, reagents or cells used in (and wastesfrom) the other manufacturing processes, and vice versa. The isolationmay be achieved by ensuring there are no conduits, air ducts, fluidlines, etc. shared between bays. Moreover, isolation can be ensured byproviding appropriately sealed entry and exit points such as doors, forexample. In one embodiment illustrated with respect to the thirdmanufacturing bay 14 d in FIG. 1, the bays 14 can be equipped with oneway entry rooms 48 and one way exit rooms 50. The entry rooms 48 can beclean rooms removably and directly connected to an entry of the bay 14via a movable corridor 49. The entry rooms 48 can be for manufacturingpersonnel to don a clean suit or other manufacturing attire, forexample, prior to entering the bay 14. The exit rooms 50 can beremovably and directly connected to the bays 14 via a movable exitcorridor 51. The exit rooms 50 can be for manufacturing personnel toexit the bay 14 into and change back into their street clothes, forexample. In some alternative embodiments, one way entry and/or exitrooms may be contained within the bay 14, or may be attached to (e.g.,adjacent to, exterior to) the core 12, as will be described below withreference to the various embodiments depicted in FIGS. 4-6.

The manufacturing bays 14 may be of different sizes and shapes based oncapacity and/or technology. As mentioned, the bays 14 are adapted to beremovably connected to the core 12, and to be movable. Mobility can beaccomplished via rails, wheels, tracks, lifting and placement (e.g., bya crane, a crane on an overhead rail system, etc.), airlift, hovercraftor other air cushion, or by other means known in the art. In someembodiments, the bays 14 could be self-propelled or towed. The bays 14optionally comprise sealable access points 26, optionally with one-wayaccess of materials and personnel, that permit employees and rawmaterials or manufactured product to enter and exit the bays 14,optionally with decontamination areas. Each bay may also be designed forviewing by visitors, and as such could be equipped with windows ortransparent walls.

In any of the foregoing embodiments, optionally the movablemanufacturing bays 14 are not connected to each other. In someembodiments, the movable manufacturing bays 14 are sealed from the core12, except for the supply of the three [two?] or more utilities.Preferably, as depicted in FIG. 1, the core 12 has one or more sealableoutlets 30 for supplying utilities to each of the respectivemanufacturing bays 14. Accordingly, each bay 14 has at least onesealable inlet 32 for receiving the utilities from the core 12.Preferably, the core 12 is sealed from receiving incoming material fromthe movable manufacturing bays 14. This one-way communication can beachieved by using a one-way valve, for example, disposed at the outlets30 or any other means known in the art.

As depicted with reference to the fifth manufacturing bay 14 e in FIG.1, some embodiments of the manufacturing system may comprise first andsecond outlets 30 a, 30 b associated with the core 12 for each bay 14.Each of the first and second outlets 30 a, 30 b discharge, or areadapted to discharge, at least one of the utilities. This embodimenttherefore requires at least one first inlet 32 a and one second inlet 32b associated with the movable manufacturing bay 14 e. The at least onefirst inlet 32 a is removably coupled, or adapted to be removablycoupled, to the first outlet 30 a of the core 12. Similarly, the atleast one second inlet 32 b is removably coupled, or adapted to beremovably coupled, to the second outlet 30 b of the core 12. Inadditional embodiments, each of the first and second outlets 30 a, 30 bof the core 12 can comprise a plurality of outlets, each of theplurality of outlets supplying, or adapted to supply, a distinct utilityof the three or more utilities. In such embodiments, the first inlet 32a of each movable manufacturing bay 14 comprises a plurality of inletsremovably coupled, or adapted to be removably coupled, to the pluralityof outlets of the first outlet 30 a of the core 12, each of theplurality of inlets of the first inlet receiving, or adapted to receive,a distinct utility from one of the plurality of outlets of the firstoutlet. Correspondingly, the second inlet 32 b of each movablemanufacturing bay 14 comprises a plurality of inlets removably coupled,or adapted to be removably coupled, to the plurality of outlets of thesecond outlet 30 b of the core 12, each of the plurality of inlets ofthe second inlet receiving, or adapted to receive, a distinct utilityfrom one of the plurality of outlets of the second outlet 30 b.

Examples of utilities supplied from the core 12 include clean air,untreated air, sterile water, purified water (WFI or water forinjection), untreated water (for cooling or other uses not requiringsterility), specialty gases, e.g. oxygen, carbon dioxide, nitrogen,argon, helium, electricity, liquid coolant, steam, communications (e.g.,telephone, data) and/or heat. Moreover, in some embodiments, the core 12can accommodate one or more HVAC systems for different air handlingmodes (e.g., Class 100-100,000), computers for monitoring, monitoringequipment, generators, backup generators, and optionally a duplicatesystem for supplying such utilities to ensure no loss of productivity ifa breakdown occurs. A duplicate system also allows an increase capacityif needed.

In some embodiments, each individual bay 14 can be equipped with its ownHVAC air-handling unit, instead of or in addition to, a central HVACair-handling unit stationed in the core 12. Such individual HVAC unitscould be 2 or 3 phase units, operating at 220 or 230 volts, for example,and sized depending the dimensions of the bays 14. In such anembodiment, the individual HVAC units could easily be serviced when thebays 14 are disconnected from the core 12 without interrupting themanufacturing process or processes being conducted in the other bays 14.Furthermore, in some embodiments, each bay 14 could be equipped with itsown back-up electrical generator for use under circumstances where themain electricity supplied from the core 12 is interrupted. In otherembodiments, all of the utilities, but for a primary source of water andelectricity can be maintained on each of the bays 14 themselves withinutility rooms 23, for example, only one of which is depicted withreference to the fifth bay 14 e in FIG. 1. Such utility rooms 23 can besealed from the respective workspaces 20 of the bays 14, while the waterand electricity can be supplied to the bays 14 in any of the mannersdescribed herein.

In some embodiments, the first, second or more facilities 22respectively comprise a plurality of components 34 (shown in the firstand second manufacturing bays 14 a, 14 b in FIG. 1). Each of thecomponents 34 performs one or more steps of a chemical, a biological, ora pharmaceutical manufacturing process. Embodiments of manufacturingprocesses, or portions or steps of manufacturing processes, that the oneor more components 34 can perform include but are not limited to one orpreferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or more ofthe following:

-   cell inoculum preparation;-   culturing or fermentation of mammalian cells such as Chinese hamster    ovary (CHO) cells, mouse myeloma cell lines, human embryonic kidney,    human retinal cells, NS0, HEK293, PER.C6, or cells suitable for    replicating viruses, such as African green monkey VERO, MDCK (canine    kidney cells), CEF (chicken embryonic fibroblasts), 2BS, Mark145,    ST1, DF-1, CIK, EPC;-   incubation of chicken eggs for vaccine production;-   culturing or fermentation of bacterial or prokaryotic cells,    including but not limited to gram-negative or gram-positive    organisms, Enterobacteriaceae such as E. coli, e.g. E. coli K12    strain, E. coli X1776 strain, E. coli W3110 strain, and E. coli K5,    Enterobacter, Pseudomonas such as P. fluorescens and P. aeruginosa,    Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella    typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as    well as Bacilli such as B. subtilis and B. licheniformis, or    Streptomyces; culturing fermentation of yeast or fungal cells,    including but not limited to Saccharomyces, e.g. S. cerevisiae,    Schizosaccharomyces pombe, Kluyveromyces, Pichia, e.g. P. pastoris,    Candida, Trichoderma, Neurospora, e.g. N. crassa, Schwannomyces,    filamentous fungi such as, e.g., Neurospora, Penicillium,    Tolypocladium, neosporidia, Aspergillus, e.g. A. nidulans and A.    niger, Hansenula, Kloeckera, Torulopsis, or Rhodotorula;-   culturing insect cells, e.g. baculoviral systems, Sf9 cells;-   growing plant cells, including but not limited to algae, tobacco,    algae, duckweed, or mushrooms;-   inoculating cells or chicken eggs with virus;-   harvesting cells or virus or culture medium;-   inactivated vaccine production, including but not limited to heat    killed pneumococcal or formalin-treated viruses, live vaccine    production, including replication of influenza, or other viruses for    vaccines, e.g. measles, mumps, rubella, varicella, polio, rabies,    H5N1 virus;-   viral vector production, including but not limited to adenovirus,    AAV, alphavirus, poxvirus, retrovirus, picornavirus, paramyxovirus,    rhabdovirus;-   counting cells, cell viability measurement, osmolarity measurement,    metabolite measurement, lactate dehydrogenase measurement;-   lysing cells;-   centrifugation processes;-   filtration processes;-   freezing processes, including freezing of purified bulk product;    thawing processes;-   purification processes, including but not limited to ion exchange    chromatography, affinity chromatography, hydrophobic interaction    chromatography, hydrophobic charge induction chromatography, size    exclusion chromatography, metal affinity chromatography, protein A    chromatography, hydroxyapatite separation, multicolumn    countercurrent solvent gradient purification process,-   buffer dilution processes, formulation and/or filing processes,    including but not limited to adding excipients, sterile filtration,    filling processes, freeze-drying, spray-drying, pegylation, sealing,    labeling, process control, liquid nitrogen storage;-   peptide synthesis and/or purification processes;-   siRNA synthesis and/or purification processes;-   synthesis and/or purification of small organic molecules. Where such    manufacturing processes are portions of steps of an overall    manufacturing processes to produce a final product or intermediate    product, the product of such a portion or step is referred to herein    as a “stage of manufacture.”

Some embodiments of components 34 for carrying out such manufacturingprocesses, or portions or steps of manufacturing processes, include butare not limited to one or preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16 or more of the following: a culturing component, aharvesting component, a purifying component, a biosafety cabinet, one ormore culture flasks, an incubator, a carbon dioxide incubator, a cellcounter, a cell viability measuring device, an osmolarity measuringdevice, a metabolite measuring device, a lactate dehydrogenase measuringdevice, a sealer, sterile connecting devices, a microscope, a waterbath, a peristaltic pump, a bioreactor, including single use ordisposable bioreactors, a wave bioreactor, a media batch tank, a bufferholding tank, an agitator, a sparger, a light house for plants, a tankfor growing algae/duckweed, a room for mushrooms, a pump, a piston pump,a diaphragm pump, a rotary lobe pump, a positive displacement pump, aflow control valve, a centrifuge component, a disk stack centrifuge, apressure regulator, a surge tank, a cell lysis component, a mechanicaldisruptor, a shredder and/or extractor and/or vacuum system forseparating proteins from plants, algae or mushrooms, a depth filtercomponent, a clarification filter, a holding tank, an ultrafiltrationcomponent, a diafiltration component, an ultrafiltration/diafiltrationsystem, a drain line, a heat removal component, a recirculation tankjacket, a heat exchanger, a laminar flow hood, a freezing system, one ormore cryovessels, one or more cold baths, one or more liquid nitrogensystems, one or more freeze/thaw components, a spray-dryer, afreeze-dryer, a buffer dilution skid, an ion exchange chromatographycolumn or membrane or skid or bed, an affinity chromatography column ormembrane or skid or bed, a hydrophobic interaction chromatography columnor membrane or skid or bed, a hydrophobic charge inductionchromatography column or membrane or skid or bed, a liquidchromatography column or membrane or skid or bed, a high pressure liquidchromatography column or membrane or skid or bed, a gas chromatographycolumn or membrane or skid or bed (for both separation of organicmolecules and for analysis), other separation technologies, a sizeexclusion chromatography column or membrane or skid or bed, a metalaffinity chromatography column or membrane or skid or bed, a protein Achromatography column or membrane or skid or bed, a hydroxyapatitecolumn or membrane or skid or bed, disposable purification systems,process control systems, a filter housing, an ultraviolet analyzer, aconductivity probe, a steam seal, a steam trap, a glasswasher, anautoclave, a sterilizing filter, one or more sterile containers, one ormore sterile vials, one or more sterile syringers, a lyophilizer, a fumehood (optionally connected to an outlet in the bay) and relatedequipment for chemical synthesis, an evaporator for removing solvents(optionally connected to an outlet in the bay), a crystallization systemfor purifying organics, one or more computer networks for individualbays and for the core facilities, one or more analytical devices forassaying products, electrophoresis equipment (eg, SDS-PAGE), a pH meter,a mass spectrometer, an IR spectrometer, a UV spectrophotometers (foranalysis or detection during processing), in-line analytics attached tofermentation and purification systems, disposable fermentation systemsfrom 20 L-5000 L or more using stir (e.g., Xcellerex) or movement (e.g.,GE Healthcare Wave), centrifugation equipment for either discontinuousor continuous separation, clean air hoods or containment systems forfilling, wiring for or wireless systems for monitoring or automatedprocesses, gas lines for clean air or specialty gases, water lines,pumps for fluid transfer, containers for product collection, freezer andcold room areas, non-aqueous solvent storage systems, control systemsand specialty software for automation and apparatus controls.

Other embodiments of components 34 for carrying out such manufacturingprocesses, or portions or steps of manufacturing processes, include butare not limited to one or preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16 or more of the following: a culturing component, aharvesting component, one or more culture flasks, an incubator, a carbondioxide incubator, a cell counter, a bioreactor, a media batch tank, acell lysis component, an autoclave, a sterilizing filter, andelectrophoresis equipment such as an SDS-PAGE.

Other embodiments of components 34 for carrying out such manufacturingprocesses, or portions or steps of manufacturing processes, include butare not limited to one or preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16 or more of the following: a purifying component, abiosafety cabinet, a sparger, a mechanical disruptor, an ultrafiltrationcomponent, a diafiltration component, an ultrafiltration/diafiltrationsystem, a laminar flow hood, one or more cryovessels, an ion exchangechromatography column or membrane or skid or bed, an affinitychromatography column or membrane or skid or bed, a hydrophobicinteraction chromatography column or membrane or skid or bed, ahydrophobic charge induction chromatography column or membrane or skidor bed, a size exclusion chromatography column or membrane or skid orbed, a metal affinity chromatography column or membrane or skid or bed,a protein A chromatography column or membrane or skid or bed, ahydroxyapatite column or membrane or skid or bed, a liquidchromatography column or membrane or skid or bed, a high pressure liquidchromatography column or membrane or skid or bed, a gas chromatographycolumn or membrane or skid or bed, a lyophilizer, one or more extractorsystems, one or more evaporators each with an outlet in the bay,crystallization systems for purifying organics, one or more in-lineanalytics attached to fermentation and purification systems, and one ormore disposable fermentation systems.

In some embodiments, the components 34 can include a hood for asepticprocessing, wherein the hood has one, two, three or all organism countsselected from the group consisting of: (a) viable particulate airorganism count of <1 CFU/m³, (b) settling plate organism count of <1CFU/4 hours, (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of <1 CFU/plate, and (d) touch plate organism countof <1 CFU/plate. In such embodiments, some methods of using themanufacturing system could include maintaining the hood to have one,two, three or all organism counts selected from the group consisting of:(a) viable particulate air organism count of <1 CFU/m³, (b) settlingplate organism count of <1 CFU/4 hours, (c) Replicate OrganismsDetection and Counting (RODAC) plate organism count of <1 CFU/plate, and(d) touch plate organism count of <1 CFU/plate.

In some embodiments, the components 34 can include a surface (e.g.,wall, floor, counter and/or sink) or area, e.g., for aseptic processing,wherein the surface has one, two, three or all organism counts selectedfrom the group consisting of: (a) viable particulate air organism countof ≤10 CFU/m³, (b) settling plate organism count of ≤5 CFU/4 hours, (c)Replicate Organisms Detection and Counting (RODAC) plate organism countof ≤5 CFU/plate, and (d) touch plate organism count of ≤5 CFU/plate. Insuch embodiments, some methods of using the manufacturing systems couldinclude maintaining the surface to have one, two, three or all organismcounts selected from the group consisting of: (a) viable particulate airorganism count of ≤10 CFU/m³, (b) settling plate organism count of ≤5CFU/4 hours, (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of ≤5 CFU/plate, and (d) touch plate organism countof ≤5 CFU/plate.

In still further embodiments, the components 34 can include a surface(e.g., wall, floor, counter and/or sink) or area, e.g., for fermentationand/or purification processes, wherein the surface has one, two, threeor all organism counts selected from the group consisting of: (a) viableparticulate air organism count of ≤100 CFU/m³, (b) settling plateorganism count of ≤50 CFU/4 hours, and (c) Replicate Organisms Detectionand Counting (RODAC) plate organism count of ≤25 CFU/plate. In suchembodiments, some methods for using the manufacturing system couldinclude maintaining the surface to have one, two, three or all organismcounts selected from the group consisting of: (a) viable particulate airorganism count of ≤100 CFU/m³, (b) settling plate organism count of ≤50CFU/4 hours, and (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of ≤25 CFU/plate.

In some embodiments, each movable manufacturing bay 14 comprises acontrol system for controlling the associated manufacturing processindependent of the manufacturing processes carried out in the other bays14. Such a control system can include a central processor, a memorydevice, one or more user interfaces, any number of sensors foridentifying various process parameters within the bays, and/or any othercontrol system components that may be desirable.

In some embodiments, each of the movable manufacturing bays 14 furthercomprises a drain 38 (shown in FIG. 2) for discharging waste generatedduring the associated manufacturing processes. In one embodiment, thewaste is discharged into a waste receptacle 44, as shown in FIG. 2. Thewaste receptacle 44 may include a self-contained waste holding tank, asystem of pipes for delivering waste to a sewage system, a central wastetreatment and disposal control mechanism, or any other foreseeableconstruction. In some embodiments, gravity-assisted flow permits thewaste from each bay 14 to exit the drain 38 and flow to the wastereceptacle 44 that is located below (e.g., one floor below) the bays 14,where the waste can be decontaminated, treated, and/or processed, etc.The drain 38 and waste receptacle 44 are preferably isolated from thecore 12, so as to avoid contamination of the core 12. The drain 38 ofeach of the bays 14 can be equipped with a one-way check valve, a trap,or a similar flow control device to handle condensable gases, forexample. In other embodiments, condensers (e.g., surface condensers) canbe used to remove emissions, such as volatile organic compoundemissions. Moreover, in some embodiments, the drain 38 can include acap, for example, for sealing the drain 38 when the bay 14 is beingtransported.

As mentioned above, in some embodiments, the manufacturing system 10also comprises the housing 16. The housing 16 of the embodiment shown inFIG. 1 contains the core 12, the first through sixth movablemanufacturing bays 14 a-14 f that are connected, or connectable, to thecore 12, and any additional manufacturing bays 14 that may be laterconnected to the core 12. In some embodiments, the system also comprisesa holding area 24, which may be disposed inside or outside of theoptional housing 16. The holding area 24 is preferably disposed awayfrom the core 12 and provides a location where each of the movablemanufacturing bays 14 can be positioned to undergo (i) a cleaningoperation, whereby the workspaces of the first and second movablemanufacturing bays are cleaned, (ii) a change-over operation, wherebythe facilities of the first and second movable manufacturing bays arealtered, (iii) qualifying, preparation and loading of supplies andspecific raw materials (including reagents, cells and/or disposablemanufacturing components) for the next manufacturing process, and/or(iv) a servicing operation on any of the facilities 22, utilities, or anHVAC unit associated with the bays 14. For example, as depicted in FIG.3, one embodiment of the holding area 24 can include a clean area 42,for introducing clean raw materials and/or utilities to one or more bay14, and/or one or more dirty areas (not depicted), for decontaminatingor cleaning a bay. The clean and/or dirty areas may themselves include awalled-off section of the holding area 24 with openings or passages thatare adapted to be removable coupled to one or more access points of thebays 14. Such a configuration ensures that no cross-contamination canoccur between the dirty area and the clean area.

As depicted in FIG. 3, the manufacturing system 10 can optionallycomprise or be disposed adjacent to auxiliary stations 40 such asanalytical laboratories that are capable of separately handling multiplesample types, a warehouse including shipping and receiving areas,equipment storage area, a cell bank storage area, large capacityfreezers, e.g., 2-8 degrees Centigrade, or −20 degrees Centigrade, or−70 degrees Centigrade, offices or administrative space, conferencerooms, auditoriums, process and formulation labs, and/or other researchor development laboratories or facilities. In certain embodiments, themanufacturing system may comprise the core, bays, holding area andauxiliary stations within the same housing structure.

In a related aspect, the invention provides methods of using themanufacturing systems 10 to manufacture a plurality of products,preferably in parallel, and preferably using a plurality of distincttechnologies. In some embodiments, the invention provides a method ofmanufacturing a plurality of products that first includes connecting thefirst movable bay 14 a to the core. Then, the method includes performinga first manufacturing process with a first configuration of components34 disposed within the first movable bay 14 a to manufacture a firstproduct. Then, the first movable bay 14 a is disconnected from the core12, and a second configuration of components 34 can be establishedwithin the first movable bay 14 a. Next, the first movable bay 14 a isreconnected to the core 12, and a second manufacturing process isperformed with the second configuration of components 34 to manufacturea second product. In some instances, the second manufacturing process isdistinct from the first manufacturing process. Moreover, in someinstances, the time period required for disconnecting the first movablebay 14 a from the core 12, establishing the second configuration ofcomponents 34, and reconnecting the first movable bay 34 to the core 12can be 30 days or less, 28 days or less, 21 days or less, 14 days orless, 10 days or less, 5 days or less, or 4 days or less, or 3 days orless, or 2 days or less, or 1 day or less, for example.

In some embodiments, the method can further include supplying at leastone utility to the first movable bay 14 a from the core 12 when thefirst movable bay 14 a is connected to the core 12. The at least oneutility includes at least one of the utilities, preferably selected fromthe group consisting of (a) clean air, (b) clean water, (c) oxygen, and(d) carbon dioxide. Other utilities described hereinabove may besupplied, or any other foreseeable utility. In some embodiments, threeor more utilities, preferably selected from the group consisting of (a)clean air, (b) sterile water, (c) electricity, (d) oxygen, and (e)carbon dioxide are supplied to the first movable bay 14 a from the core12. Optionally, further utilities may be supplied, including but notlimited to any of the utilities described herein.

In some embodiments, connecting the first movable bay 14 a to the core12 includes connecting at least one 32 inlet of the first movable bay 14a to at least one outlet 30 of the core 12, wherein the at least oneoutlet 30 of the core 12 supplies at least one utility, preferablyselected from the group consisting of (a) clean air, (b) clean water,(c) oxygen, and (d) carbon dioxide. In some embodiments, disconnectingthe first movable bay 14 a from the core 12 comprises disconnecting theat least one inlet 32 of the first movable bay 14 a from the at leastone outlet 30 of the core 12. In some embodiments, re-connecting thefirst movable bay 14 a to the core 12 comprises re-connecting the atleast one inlet 32 of the first movable bay 14 a to the at least oneoutlet 30 of the core 12. In some embodiments, connecting the at leastone inlet 32 of the first movable bay 14 a to the at least one outlet 30of the core 12 comprises connecting a plurality of outlets 30 of thecore 12 to a plurality of inlets 32 of the first movable bay 14 a,wherein each of the plurality of outlets 30 supplies a distinct utility.In some embodiments, disconnecting the at least one inlet 32 of thefirst movable bay 14 a from the at least one outlet 30 of the core 12comprises disconnecting the plurality of inlets 32 from the plurality ofoutlets 30. In some embodiments, re-connecting the at least one inlet 32of the first movable bay 14 a to the at least one outlet 30 of the core12 comprises re-connecting the plurality of inlets 32 to the pluralityof outlets 30.

Optionally, the method further comprises moving the first movable bay 14a to the holding area 24 after disconnecting the first movable bay 14 afrom the core 12 and prior to establishing the second configuration ofcomponents 34. Then, the first movable bay 14 a is returned to the core12 prior to re-connecting the first movable bay 14 a thereto. In someembodiments, the method further comprises cleaning the first movable bay14 a while it is located in the holding area 24 and prior toestablishing the second configuration of components 34. In someembodiments, the method further comprises connecting the second, third,fourth, fifth, or sixth movable bays 14 b-14 f to the core 12 while thefirst movable bay 14 a is connected to the core 12 without connectingany of the second, third, fourth, fifth, or sixth movable bays 14 b-14 fto the first movable bay 14 a.

Preferably, performing each of the manufacturing processes in each bay14 comprises performing one or more of a chemical, a biological, and apharmaceutical manufacturing process. Embodiments of manufacturingprocesses include but are not limited to one or preferably 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or more of any of themanufacturing processes described hereinabove, as well as any othermanufacturing process not specifically described hereinabove.

In some embodiments, the method further comprises performing a third,fourth, fifth, and/or sixth manufacturing process within the second,third, fourth, fifth, and sixth movable bays 14 b-14 f in parallel withperforming the first manufacturing process within the first movable bay14 a. In some embodiments, the third manufacturing process is distinctfrom the first manufacturing process. Thus, it should be appreciatedthat the invention advantageously provides a flexible system whereby asingle movable manufacturing bay 14, whether it be the first, second,third, fourth, fifth, or sixth bay 14 b-14 f described herein, or anyother bay, can be easily connected and disconnected from the core 12such that different manufacturing processes can be carried out thereinwith different configurations of manufacturing components 34.

In another aspect, the invention provides a method of manufacturing aplurality of products that includes connecting the first movable bay 14a to the first dock position 18 a of the core 12, whereby the first dockposition 18 a is first selected from the plurality of dock positions 18a-18 f. Then, a first manufacturing process is performed with aconfiguration of components 34 disposed within the first movable bay 14a to manufacture a first product. Then, the first movable bay 14 a isdisconnected from the first dock position 18 a of the core 12, and adifferent (e.g., second, third, fourth) movable bay 14 is connected tothe first dock position 18 a. A manufacturing process is then performedwith a configuration of components 34 disposed within the differentmovable bay 14 to manufacture a different product or a same product. Insome instances, the time period required for disconnecting the firstmovable bay 14 a from the first dock position 18 a and connecting thedifferent movable bay 34 to the first dock position 18 a can be 48 hoursor less, or 36 hours or less, or 24 hours or less, or 12 hours or less,or 8 hours or less, for example. In some other instances, the timeperiod required for disconnecting the first movable bay 14 a from thefirst dock position 18 a, connecting the different movable bay 34 to thefirst dock position 18 a, and beginning to perform the manufacturingprocess to manufacture the different products can be 48 hours or less,or 36 hours or less, or 24 hours or less, or 12 hours or less, or 8hours or less, for example.

With this method, it should be appreciated that the system 10 of thepresent disclosure provides the flexibility of being able to quicklyswitch from manufacturing one product in the first bay 14 a tomanufacturing a different (or same) product in a different bay 14without having to reconfigure (or clean) the components 34 in the firstbay 14 a. This can reduce manufacturing downtime and increase theoverall productivity of the system 10.

In some embodiments, the method further comprises supplying at least oneutility from the core 12 to the movable bays 14 when the movable bays 14are connected to the core 12. The at least one utility is preferablyselected from the group consisting of (a) clean air, (b) sterile water,(c) oxygen, and (d) carbon dioxide. Further utilities can be supplied,including those discussed hereinabove. In other embodiments, three ormore of the utilities, preferably selected from the group consisting of(a) clean air, (b) clean water, (c) electricity, (d) oxygen, and (e)carbon dioxide, are supplied from the core 12 to the movable bays 14when the movable bays 14 are connected to the core 12. Optionally,further utilities may be supplied, including but not limited to any ofthe utilities described herein. Moreover, in this method, the movablebays 14 can be connected and disconnected from the core 12 in any of themanners described hereinabove with the previous method, or in any othermanner known in the art. Furthermore, identical to that described above,performing each of the manufacturing processes comprises performing oneor more of a chemical, a biological, and a pharmaceutical manufacturingprocess or portions or steps of manufacturing processes. Embodiments ofmanufacturing processes include but are not limited to one or preferably2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or more of any of themanufacturing processes described herein.

In yet another related aspect, the invention provides a method ofmanufacturing that includes selecting the first bay 14 a from aplurality of available bays 14 a-14 f. The first bay 14 a is then movedadjacent to the core 12 and removably connected thereto. Next, thesecond bay 14 b is selected from the plurality of available bays 14 a-14f and moved adjacent to the core 12. The second movable bay 14 b is thenremovably connected to the core 12. With the first and second movablebays 14 a, 14 b removably connected to the core, a first manufacturingprocess is performed with the components 34 disposed within the firstbay 14 a to manufacture a first product, and a second manufacturingprocess is performed in parallel with the first manufacturing processwith the components 34 disposed within the second bay 14 b tomanufacture a second product.

It should be appreciated that this method provides the advantage ofenabling manufacturing personnel to select one or more bays 14 from anynumber of available bays for performing multiple process in parallel.The number of available bays is limitless. The number of manufacturingprocesses that may be performed in parallel is only limited by thespecific design and configuration of the core 12 and the capacity of thecore 12 to supply utilities. The remainder of the system and the meansfor connecting and disconnecting the bays 14 are the same as thosediscussed above.

In some embodiments, the method further comprises controlling the firstmanufacturing process with a first control system associated with thefirst bay 14 a, and controlling the second manufacturing process with asecond control system associated with the second bay 14 b. In thisconfiguration, the first and second control systems can be distinctcontrol systems. In some embodiments, the second manufacturing processis controlled independently of the first manufacturing process.

In yet another aspect, the invention provides a method of manufacturingthat includes selecting a first bay 14 a and a second bay 14 b from aplurality of available bays 14 a-14 f and utilizing the first and secondbays 14 a, 14 b to perform sequential portions of a single manufacturingprocess. After selection, the first and second bays 14 a, 14 b are movedto the core 12 and removably coupled thereto. With the first movable bay14 a coupled to the core 12, a product undergoes a first portion of amanufacturing process with the components 34 stored in the first bay 14a to bring the product to a first stage of manufacture. The product inthe first stage of manufacture is then transferred to the second bay 14b. With the second bay 14 b coupled to the core 12, the productundergoes a second portion of the manufacturing process with thecomponents 34 stored in the second bay 14 b to bring the product to asecond stage of manufacture.

In still another aspect, the invention provides a method ofmanufacturing that includes selecting a first bay from a plurality ofavailable bays 14 a-14 f, moving the first bay 14 a to the core 12, andremovably coupling the first bay thereto. With the first movable bay 14a coupled to the core 12, a product undergoes a first portion of amanufacturing process with the components 34 stored in the first bay 14a to bring the product to a first stage of manufacture. Then, the methodincludes selecting a second bay 14 b from the plurality of availablebays 14 a-14 f, moving the second bay 14 b to the core 12, and removablycoupling it thereto. With the second bay 14 b coupled to the core 12,the product in the first stage of manufacture is then transferred fromthe first bay 14 a to the second bay 14 b. The product then undergoes asecond portion of the manufacturing process with the components 34stored in the second bay 14 b to bring the product to a second stage ofmanufacture.

In some embodiments, either or both of the foregoing sequentialmanufacturing methods could further include selecting a thirdmanufacturing bay 14 c from the available bays 14 a-14 f, moving thethird bay 14 c to the core 12, and coupling the third bay 14 c to thecore 12. So configured, the product in the second stage of manufactureis transferred to the third bay 14 c. With the third bay 14 c coupled tothe core 12, the product undergoes a third portion of the manufacturingprocess with the components 34 stored in the third bay 14 c to bring theproduct to a third stage of manufacture.

By the foregoing, it should be appreciated that the use of the termsfirst, second, and third portions of manufacturing processes and first,second, and third stages of manufacture are only used to express therelative order of these processes or stages, and that each may beintermediate to an overall process or progression through multiplestages.

It should be appreciated that in some aspects of the methods described,the overall manufacturing process is divided into a plurality ofportions, wherein each portion is performed in a separate and distinctmanufacturing bay 14 sequentially, for example. In contrast, in otheraspects of the methods described, the overall manufacturing process isperformed in a single bay 14. In some embodiments, however, the singlebay 14 could be separated or subdivided into a plurality of differentsections divided from each other by movable or openable partitions suchas doors, walls, curtains, etc. So configured, the various portions ofthe overall manufacturing process can be performed in isolated areas ofeach individual bay, if desired. Any one of the foregoing types ofprocesses is within the scope of the present application, and thepractical application of the invention will depend on the specificproduct being manufactured, as well as the quantity being manufactured.

For example, in some embodiments, the invention provides a method ofmanufacturing 500 liters of product (e.g., culture supernatantcontaining unpurified product), wherein the first bay 14 includescomponents 34 for culturing such that the first stage of manufactureincludes cultured cells of the product. The cultured cells of theproduct can then be transferred to the second bay 14 b for fermentingsuch that the second stage of manufacture comprises fermented product.The fermented product can then be transferred to the third bay 14 c forpurification such that the third stage of manufacture comprises purifiedproduct. This can be the end of the manufacturing process. In otherembodiments, more or less than 500 liters of product can bemanufactured. For example, in one embodiment, 2000 liters of productcould be manufactured. The increased volume could foreseeably requirethe manufacturing process to be divided into one or more additionalportions requiring, for example, one or more additional separate bays14.

For example, when manufacturing 2000 liters of product, the culturedproduct produced in the first bay 14 a can be transferred to the secondbay 14 b to undergo a pre-viral purification portion of the overallmanufacturing process such that the second stage of manufacturecomprises a pre-viral purified product. The pre-viral purified productcan then be transferred to the third bay 14 c for undergoing apost-viral purification portion of the overall manufacturing process,thereby resulting in a post-viral purified product. The post-viralpurified product can then be transferred to a fourth bay 14 d, which hasalready been selected from the available bays 14 a-14 f and coupled tothe core 12, for undergoing a further purification portion of theprocess such as to yield purified product. The purified product can bethe final end product.

In some embodiments, the method further includes any number of theadditional process steps discussed hereinabove. Various structuressuitable for transferring an intermediate product or stage ofmanufacture from one bay to another bay are described below.

While the manufacturing system 10 of the present disclosure has thus farbeen described as optionally including externally located entry and exitrooms 48, 50 for providing controlled access to the bays 14, asillustrated in FIG. 1, alternative embodiments could be configured toinclude different mechanisms for controlling access to the bays 14.

For example, FIG. 4 illustrates one alternative embodiment of a system100 constructed in accordance with the present disclosure, and includingone or a plurality of clean connect areas 149, which are coupled (e.g.,removably, fixedly) to a core 112. In some embodiments, one cleanconnect area 149 is disposed adjacent to a movable manufacturing bay114. In other embodiments, one or more clean connect areas 149 aredisposed adjacent to one or more movable manufacturing bays 114. In theembodiment depicted in FIG. 4, the system 100 includes first througheighteenth clean connect areas 149 a-149 r and a corresponding firstthrough eighteenth movable bays 114 a-114 r. The clean connect areas 149a-149 r are generic and not specifically assigned to any one bay 114. Assuch, one clean connect area 149 a-149 r can serve any one of the bays114 a-114 r. In some embodiments, the core 112 is rectangular in shapeand the bays 114 a-114 r connect thereto along each side in a lineararrangement. With the exception of its shape, the core 112 can beidentical to and include each and every feature of the core 12 describedabove with reference to FIGS. 1-3. Additionally, each of the bays 114a-114 r define workspaces 120 accommodating facilities 122 forperforming manufacturing processes and can be identical to and includeeach and every feature of the bays 14 described above with reference toFIGS. 1-3. Accordingly, each and every feature of the core 112 and bays114 a-114 r depicted in FIG. 4 will not be repeated.

Similar to the entry and exit rooms 48, 50 described above withreference to FIG. 1, the clean connect areas 149 a-149 r of the system100 depicted in FIG. 4 can be adapted to control access to and from therespective bays 114 a-114 r. As such, each clean connect area 149 a-149r generally includes a square or rectangular structure defining aselectively sealable room positioned between a corresponding one of thebays 114 a-114 r and a corridor (e.g., one of two primary corridors 101a, 101 b), through which operating personnel can pass into and out ofthe clean connect areas 149 a-149 r. In the disclosed embodiment, theprimary corridors 101 a, 101 b extend as part of and along oppositesides of the core 112 and are sealed therefrom such that personnelcannot pass between the core 112 and the primary corridors 101 a, 101 b.In other embodiments, the primary corridors 101 a, 101 b could belocated at a position spaced away from the core 112, as depicted in FIG.7.

For example, FIG. 7 depicts a system 400 including core 412, a pluralityof movable manufacturing bays 414, and a pair of primary corridors 401a, 401 b. In general, each of these components can be constructedidentical to any of the similar components described herein, andtherefore, the details will not be repeated. Additionally, the system400 of FIG. 7 can include one or more optional housings 416 a coveringand possibly surrounding the areas occupied by the bays 414, asillustrated, or a housing 416 b could cover or surround the entiresystem 400 similar to the housing 16 described above with reference toFIG. 1. Still further, although not shown, the system 400 of FIG. 7could also be equipped to include transfer panels 190 and/or controlledcorridors 192 similar to those described above with reference to thesystem of FIG. 4 for facilitation transfer of product between the bays414 if desired.

Furthermore, similar to the systems described above, the system 400 ofFIG. 7 can be equipped with at least one holding area 424 that can bedisposed inside or outside of the one or more housings 416 a, 416 b. Theholding area 424 is preferably disposed away from the core 412 andprovides a location where each of the bays 414 can be positioned toundergo (i) a cleaning operation, whereby the workspaces of the firstand second movable manufacturing bays are cleaned, (ii) a change-overoperation, whereby the facilities of the first and second movablemanufacturing bays are altered, (iii) qualifying, preparation andloading of supplies and specific raw materials (including reagents,cells and/or disposable manufacturing components) for the nextmanufacturing process, and/or (iv) a servicing operation on any of thefacilities, utilities, or an HVAC unit associated with the bays 414.

One distinction between the system 400 depicted in FIG. 7 and the system100 depicted in FIG. 4, for example, is the configuration of the primarycorridors 401 a, 401 b relative to the core 412. That is, the primarycorridors 401 a, 401 b each extend away from the core 412 such that thebays 414 are positioned at different distances from the core 412. Inthis embodiment, the bays 414 are still coupled to the core 412 ingenerally the same manner that the bays 114 are coupled to the core 112described above with reference to FIG. 4. That is, the system 400includes conduits 415, only one of which is illustrated for the sake ofclarity, that carry utilities from the core 412 to each of the bays 414.In one preferred embodiment, the conduits carrying the utilities fromthe core 412 extend over the bays 414 and drop down to connect thereto.In other embodiments, however, the conduits can extend from the core 412in the ground or floor of the system 400, for example, such that theconduits connect beneath the bays 414. In still some other embodiments,the conduits could extend from the core 412 along the primary corridors401 a, 401 b to the bays 414, for example, or in generally any otherconfiguration. While the embodiment depicted in FIG. 7 includes theprimary corridors 401 a, 401 b extending from the core 412 in twodifferent directions, i.e., from the left and right side of the core412, this is merely an example. In some embodiments, one or more primarycorridors 401 may extend in only one direction from the core 412, twodirections (e.g., opposite) from the core 412, such as depicted in FIG.7, or three or more directions from the core 412.

While FIG. 4 includes the primary corridors 101 a, 101 b extendingadjacent to the core 112, and FIG. 7 includes the primary corridors 401a, 401 b extending away from the core 412, other systems may not includeprimary corridors 101 a, 101 b at all. As shown in FIG. 4, the primarycorridors 101 a, 101 b may be connected to each other by one or moresecondary corridors, such as for example, a pair of secondary corridors105 a, 105 b located at opposite ends of the core 112 such thatpersonnel can pass between the two primary corridors 101 a, 101 b and/orout of the system 100 entirely. Similar secondary corridors could beused in the system of FIG. 7, if desired.

As mentioned, in some embodiments, each of the clean connect areas 149a-149 r is generally square, or rectangular in shape. In one embodiment,the clean connect areas 149 a-149 r can be fixedly coupled to the core112 and each of the bays 114 a-114 r can be removably coupled to acorresponding clean connect area 149 a-149 r. That is, flat interiorwalls of the clean connect areas 149 a-149 r can be fixedly coupled tothe core 112 adjacent flat exterior walls of the corridors 101 a, 101 b,as depicted. Moreover, flat end walls of the bays 114 a-114 r can beremovably coupled to the core 112 adjacent flat exterior walls of theclean connect areas 149 a-149 r. In other embodiments, the clean connectareas 149 a-149 r can be fixedly coupled to the bays 114 a-114 r andremovably coupled to the core 112 via the corridors 101 a, 101 b. Instill further embodiments, the clean connect areas 149 a-149 r can bestructures separate from the core 112 and the bays 114 a-114 r andseparately movable. In such an embodiment, the clean connect areas 149a-149 r can be removably coupled to both the core 112 and the respectivebays 114 a-114 r.

As mentioned above, the clean connect areas 149 a-149 r serve to controlaccess to the bays 114 a-114 r. Therefore, each of the clean connectareas 149 a-149 r includes a bay entry portion 151 and a bay exitportion 153 separated and/or sealed from each other by a partition 155such as a wall, a pane of glass, etc. For the sake of clarity, thepresent embodiment of the bay entry and exit portions 151, 153 areillustrated with respect to the tenth clean connect area 149 j in FIG.4, but all of the clean connect areas 149 a-149 r could be equipped inthe same manner.

The bay entry portion 151 includes an entry point 151 a and an exitpoint 151 b. The bay exit portion 153 includes an entry point 153 a andan exit point 153 b. The entry point 151 a of the bay entry portion 151is connected to an exit point 103 b of the primary corridor 101 b andthe exit point 153 b of the bay exit portion 153 is connected to anentry point 103 a of the primary corridor 101 b. Moreover, the exitpoint 151 b of the bay entry portion 151 is connected to an entry point155 a of the tenth bay 114 j and the entry point 153 a of the bay exitportion 153 is connected to an exit point 155 b of the tenth bay 114 j.Any or all of the entry points 151 a, 153 a, 103 a, 155 a and exitpoints 151 b, 153 b, 103 b, 155 b in the clean connect areas 149 a-149r, the bays 114 a-114 r, and corridors 101 a, 101 b can includeselectively closeable passageways such as sliding doors, pivoting doors,pocket doors, pocket doors with seals, roll doors, curtains, removableor collapsible walls, or any other type of device capable of at leastproviding physical separation and optionally providing a seal such as anairtight seal when closed.

With the clean connect areas 149 a-149 r configured as described,operating personnel can enter and exit the bays 114 a-114 r in acontrolled manner to prevent contamination of the contents of the bays114 a-114 r and/or to prevent cross-contamination between the bays 114a-114 r.

For example, to enter a specific bay, e.g., the tenth bay 114 jdescribed with reference to FIG. 4, operating personnel must first enterthe system 100 via a passageway 107 in one of the secondary corridors105 a, 105 b. In some alternative embodiments, personnel may first enterthe system 100 directly via a passageway in the primary corridors 101 a,101 b. At this point, the operating personnel can still be wearingstreet clothes or something similar. In the disclosed embodiment, thesecondary corridors 105 a, 105 b can be uncontrolled spaces, i.e.,spaces that are not required to satisfy any “clean air” standards suchas those discussed above, or otherwise. From the secondary corridor 105a, 105 b, the operating personnel can enter the primary corridor 101 bthrough another passageway 109. In one embodiment, the primary corridors101 a, 101 b can be maintained to satisfy a “clean air” standard. Forexample, the primary corridors 101 a, 101 b could be maintained tosatisfy, for example, any one of the Federal Standard 209Eclassifications of air including Class 1, Class 10, Class 100, Class1,000, Class 10,000, and in some embodiments Class 100,000.

From the primary corridor 101 b, the operating personnel can passthrough the exit point 103 b of the primary corridor 101 b and the entrypoint 151 a of the bay entry portion 151 of the clean connect area 149 jto enter the bay entry portion 151. Once in the bay entry portion 151,the operating personnel can don a clean gown, clean scrubs, a cleansuit, or some other “clean” attire before entering the tenth bay 114 j.Once the operating personnel is prepared to enter the tenth bay 114 j,the operating personnel can pass through the exit point 151 b of the bayentry portion 151 and the entry point 155 a of the tenth bay 114 j andinto the workspace 120 to assist in the performance of a manufacturingprocess, a cleaning process, etc.

To exit the workspace 120 of the tenth bay 114 j, the personnel passesthrough the exit point 155 b of the tenth bay 114 j and the entry point153 a of the bay exit portion 153 of the clean connect area 149 j,thereby entering the bay exit portion 153. When disposed in the bay exitportion 153, the operating personnel can degown and exit the bay exitportion 153 of the clean connect area 149 j via the exit point 153 b ofthe bay exit portion 153 and the entry point 103 a of the primarycorridor 101 b. From the primary corridor 101 b, the personnel canreturn to one of the secondary corridors 105 a, 105 b to exit the system100, for example. Thus, the clean connect areas 149 a-149 r operate tocontrol the flow of personnel into and out of the bays 114 a-114 r toprevent contamination.

In one embodiment, each of the clean connect areas 149 a-149 r can becleaned and/or maintained to satisfy any one of the Federal Standard209E classifications of air including Class 1, Class 10, Class 100,Class 1,000, Class 10,000, and Class 100,000. Preferably, the cleanconnect areas 149 a-149 r can be maintained to satisfy the same standardclassification as that which is maintained within the respective bays114 a-114 r. For example, for bio-manufacturing, the air within theclean connect areas 149 a-149 r and the bays 114 a-114 r can bemaintained at Class 10,000, i.e., the air contains less than 10,000particles that are 0.5 microns and larger per cubic foot of air withinthe clean connect areas 149 a-149 r and the bays 114 a-114 r. Tofacilitate and maintain the air classifications in the bays 14 and cleanconnect areas 149, the HVAC air-handling system for the bays 14 can beadditionally equipped to ensure that air flows from the bays 14, throughthe clean connect areas 149, and out to the corridors 101 a, 101 b.Preferably, the pressure differential between the bays 14 and the cleanconnect areas 149, and the pressure differential between the cleanconnect areas 149 and the corridors 101 a, 101 b, would be maintained atfive hundredths of an inch (0.05″) of water, as is generally knownwithin the art. In other embodiments, wherein the bays 14 are utilizedto manufacture viruses, for example, the HVAC air-handling system can beused to ensure that air flows into the bays 14 from the corridors 101 a,101 b. So configured, the bays 14 could be equipped with filters and/orsinks that would trap any stray particles in the air and prevent themfrom escaping the controlled environment. While the air within the cleanconnect areas 149 a-149 r and the bays 114 a-114 r has thus far beendescribed as satisfying the same air classification standards, in otherembodiments, the air within the clean connect areas 149 a-149 r and thebays 114 a-114 r could be maintained at different standards.

While the clean connect areas 149 a-149 r have thus far been describedas defining bay entry and bay exit portions 151, 153 separated by apartition 155, alternative embodiments of the clean connect areas 149a-149 r can also subdivide either or both of the bay entry and exitportions 151, 153. For example, as illustrated with respect to thethirteenth clean connect area 149 m depicted in FIG. 4, one embodimentof the bay entry portion 151 could be divided into a first stage entryportion 159 a and a second stage entry portion 161 a separated by atransition divider 163. The transition divider 163 can include aselectively closeable passageway such as a sliding door, a pivotingdoor, a pocket door, a roll door, one or more curtains, or any othertype of device capable of at least providing a designated and/orphysical separation and optionally providing a seal such as an airtightseal when closed.

In such a configuration, operating personnel can first enter the firststage entry portion 159 a of the clean connect area 149 m to don a firstlevel of clean attire, e.g., clean scrubs, and then pass through thetransition divider 163 and into the second stage entry portion 161 a todon a second level of clean attire, e.g., a clean suit, over the firstset of clean attire, prior to passing into the workspace 120 of thethirteenth bay 114 m. Upon exiting the workspace 120 of the thirteenthbay 114 m, the operating personnel can remove the first and secondlevels of clean attire in the bay exit portion 153 in a manner similarto that described above with respect to the tenth clean connect area 149j.

In alternative embodiments, the bay exit portion 153 of the cleanconnect area 149 m can also be subdivided into first and second stageexit portions 161 b, 159 b separated by a transition divider 169 forenabling operating personnel to successively remove the second level ofclean attire while in the first stage bay exit portion 161 b and thefirst level of clean attire while in the second stage bay exit portion159 b.

In one embodiment, the air within the first and second stage entryportions 159 a, 161 a and the first and second stage exit portions 161b, 159 b can be maintained in accordance with the same or different airclassification standards. For example, in one embodiment, the firststage entry portion 159 a and the second stage exit portion 159 b can bemaintained at Class 100,000, while the second stage entry portion 161 aand the first stage exit portion 161 b can be maintained at Class10,000, which can be the same as the workspace 120 of the correspondingthirteenth bay 114 m, for example.

While only the thirteenth clean connect area 114 m has been described asincluding first and second stage entry portions 159 a, 161 a andoptional first and second stage exit portions 159 b, 161 b, it should beappreciated that all or some of the clean connect areas 149 a-149 r canbe arranged in such a manner. Moreover, while the bay entry and exitportions 151, 153 of the thirteenth clean connect area 149 m have eachbeen disclosed as being optionally subdivided into two stage portions,e.g., a first stage entry portion 151 a and a second stage entry portion161 a, in alternative embodiments, the bay entry and/or exit portions151, 153 of any or all of the clean connect areas 149 a-149 r could besubdivided into 3, 4, 5, 6, 7, 8, 9, 10, or any other number of stageportions.

In the embodiment depicted in FIG. 4, the provision of utilities fromthe core 112 to each of the bays 114 a-114 r must be sealed from theprimary corridors 101 a, 101 b. For example, in one form described withreference to the ninth bay 114 i depicted in FIG. 4, the utilitiessupplied from the core 112 could be provided within one or more sealedflexible conduits 193 a, 193 b passing above, below, and/or through theprimary corridor 101 a. In the depicted form, the conduits 193 a, 193 bextend from a fixed location in the core 112 where the utilitiesoriginate and terminate at a location adjacent to the respective bay 114i. So configured, the one or more conduits 193 a, 193 b also pass above,below, and/or through the associated clean connect area 149 i. Moreover,the terminal end of the one or more conduits 193 a, 193 b can beremovably connected to an external fitting of the bay 114 i with any ofthe mechanical coupling means described above with reference to FIGS.1-3 such that the bay 114 i can be removed and swapped out for otherbays in accordance with the teachings of the present disclosure.

In another embodiment, the clean connect areas 149 a-149 r or portions(e.g., subdivided sections) thereof can serve as a designated space forpersonnel to make the utility connections between the core 112 and thebays 114 a-114 r. For example, with reference to the fifth bay 114 edepicted in FIG. 4, each of the clean connect areas 149 a-149 r couldinclude selectively sealable openings 195 a, 195 b on opposing end wallsthereof. The opening 195 a on the wall adjoining the core 112 would befor receiving one or more sealed flexible conduits 193 a, 193 b from thecore 112, and the opening 195 b on the wall adjoining the bay 114 ewould be for receiving one or more sealed flexible conduits 193 a, 193 bfrom the corresponding bay 114 e. So configured, any method of attachingthe bay 114 e to the core 112 would include receiving the conduits 193a, 193 b through the respective openings. Once received, a seal such asa rubber skirt, collar, or other mechanism, for example, can be closedor constricted around the conduits 193 a, 193 b to provide an airtightseal. Thereafter, the clean connect area 149 could be brought to a stateof cleanliness and a technician, for example, positioned within theclean connect area 149 e could then connect the one or more conduits 193a, 193 b extending from the core 112 to the one or more correspondingconduits 193 a, 193 b extending from the associated bay 114 e. Soconfigured, in this embodiment, the clean connect areas 149 a-149 i canprovide a “clean” area for making the utility connections in addition toor as an alternative to providing controlled access to the bays 114a-114 i, as described above.

In general, any of the methods of using the manufacturing system 10described above with reference to FIG. 1 apply in the same manner to thesystem 100 depicted in FIG. 4. However, the methods can also be modifiedto include various features related more specifically to the cleanconnect areas 149 a-149 r. For example, one method of manufacturing aplurality of products using the system 100 depicted in FIG. 4 canfurther include connecting a first movable bay 114 to a clean connectarea 149 prior to performing a first manufacturing process in the firstmovable bay 114. Moreover, the method can include disconnecting thefirst movable bay 114 from the clean connect area 149 prior toconnecting a different, second movable bay 114 to the same position ofthe core 112. Finally, the method can further include connecting thesecond movable bay 114 to the clean connect area 149 previously occupiedby the first movable bay 114 prior to performing another, secondmanufacturing process.

In another embodiment, the method can further include connecting entrypoints 155 a of each of the first and second movable bays 114 to exitpoints 151 b of the clean connect area 149 and connecting exit points155 b of each of the first and second movable bays 114 to entry points153 a of the clean connect area 149. Moreover, the method can includedisconnecting the entry point 155 a of the first movable bay 114 fromthe exit point 151 b of the clean connect area 149 and disconnecting theexit point 155 b of the first movable bay 114 from the entry point 153 aof the clean connect area 149.

Still further, the system 100 depicted in FIG. 4 can also be adapted tofacilitate the method described above wherein the manufacturing processis broken into a plurality of sequential portions, each portion beingperformed in a separate and distinct manufacturing bay 114. For example,as discussed above, at the end of each portion of the manufacturingprocess, the product is transferred from one bay to another bay untilthe desired product or stage of manufacture is produced. As depicted inFIG. 4, each of the bays 114 are disposed side-by-side, and as such,could include corresponding transfer panels 190 for transferring theproduct between the bays 114. In FIG. 4, each of the first and secondbays 114 a, 114 b are illustrated as including a transfer panel 190 thatis aligned with the transfer panel 190 of the other bay, but it shouldbe appreciated that any or all of the bays 114 could include a similartransfer panel. In some embodiments, the transfer panels 190 couldmerely include a window, door, or other type of panel that can beopened/closed to pass product through by hand, for example. In someembodiments, the transfer panel 190 can include a sealable conduit thatextends between the first and second bays 114 a, 114 b for pumpingproduct therebetween. In some embodiments, the sealable conduits caninclude, at least in part, disposable conduits that can be replaced atthe end of each manufacturing cycle for example.

Instead of modifying the system 100 of FIG. 4 to include the transferpanels 190, another embodiment could include controlled corridors 192disposed between or extending from and connecting adjacent bays 144 tofacilitate transfer of product between the bays when performing thesequential manufacturing process. FIG. 4 identifies a single controlledcorridor 192 disposed between the third and fourth bays 114 c, 114 d,but it should be appreciated that similar controlled corridors 192 couldbe disposed between or extending from and connecting any or all of theadjacent bays 114. The air in the controlled corridors would preferablybe maintained at the same classification level as that maintained in thebays 114, i.e., preferably Class 10,000 such that manufacturingpersonnel could travel between bays 114 without compromising the cleanstate thereof. Moreover, although not depicted, each of the bays 114would require at least one door, for example, enabling passage from thebays 114 to the controlled corridor 192. As such, at the end of a firstportion of a manufacturing process performed in the third bay 114 c ofFIG. 4, for example, the manufacturing personnel could exit the thirdbay 114 c carrying or otherwise transporting the product into thecontrolled corridor 192. Once in the controlled corridor 192, the doorto the third bay 114 c would be closed and sealed, and then the door tothe fourth bay 114 d could be opened to enable the personnel to enterthe fourth bay 114 d with the product.

Referring now to FIG. 5, a further system 200 constructed in accordancewith the principles of the present disclosure is illustrated including acore 212 and a plurality of movable manufacturing bays 214 connected orconnectable to the clean connect core 212. The core 212 and the bays 214can be identical to and include each and every feature of any of thebays 14, 114 described above, and therefore, each and every feature willnot be repeated.

Similar to the system 100 described above with reference to FIG. 4, thesystem 200 includes two primary corridors 201 a, 201 b disposed alongthe core 212 and between the core 212 and the bays 214 to provideoperating personnel access to the bays 214. Additionally, similar to thesystem 100 described above with reference to FIG. 4, the system 200includes a plurality of clean connect areas 249 disposed or disposableadjacent to a corresponding plurality of the bays 214 for controllingaccess to the bays 214. Still further, although not shown, the system100 of FIG. 5 could also be equipped to include transfer panels 190and/or controlled corridors 192 similar to those described above withreference to the system of FIG. 4 for facilitation transfer of productbetween the bays 214 if desired. In FIG. 5, the system 200 includesfirst through fifth movable bays 214 a-214 e coupled to a correspondingfirst through fifth clean connect areas 249 a-249 e. A sixth cleanconnect area 249 f coupled to the core 212 remains open and availablefor being coupled to another movable bay 214. While the system 200 inFIG. 5 only includes six clean connect areas 249 coupled to the core212, this is only an example, the system 200 could include any number ofclean connect areas 249. Unlike the system 100 described with referenceto FIG. 4, however, each of the clean connect areas 249 of the system200 depicted in FIG. 5 includes a male component 271 and a femalecomponent 273. In FIG. 5, the male and female components 271, 273 of theclean connect areas 249 are illustrated schematically to convey thegeneral concept. Any practical embodiment of such components 271, 273may not necessarily assume the form depicted, especially in terms ofshape, scale, dimension, proportion, etc.

Each of the male components 271 is fixedly connected to one of theplurality of movable manufacturing bays 214. Each of the femalecomponents 273 is fixedly connected to the core 212, adjacent to one ofthe primary corridors 201 a, 201 b. In alternative embodiments, the malecomponents 271 can be fixedly coupled to the core 212 and the femalecomponents 273 can be fixedly coupled to the bays 214. As such, when abay 214 is coupled to the core 212, a tongue 271 a of the male component271 of the clean connect area 249 is disposed within a recess 273 a inthe female component 273 to interlock the bay 214 to the core 212. Suchinterlocking configuration of the male and female components 271, 273 ofthe clean connect areas 249 can assist in properly aligning the bays 214to the core 212 to ensure that any connections for the utilitiessupplied from the core 212 can properly align with connections carriedby the bays 214 and/or clean connect areas 249. To facilitate thepassage of operating personnel between the male component 271 and thefemale component 273, each can be equipped with entry and exit pointssimilar to the entry and exit points between the clean connect areas 149and bays 114 described above with reference to the system 100 depictedin FIG. 4. Therefore, the details will not be repeated. Other featuresand characteristics of the clean connect areas 249 can be identical toand include each and every feature of the clean connect areas 149described above, and therefore, will not be repeated.

With continued reference to FIG. 5, the two corridors 201 a, 201 b ofthe system 200 are connected to a controlled area 279, which is in turnconnected to an uncontrolled area 281. A “controlled area,” as usedherein, means an area that is maintained to satisfy a “clean air”standard such as one of the clean air standards discussed hereinabove.As such, an “uncontrolled area,” as used herein, is an area that is notmaintained in accordance with a “clean air” standard. The uncontrolledarea 281 can be further connected to one or more changeover facilities283 via controlled and/or uncontrolled corridors 285. The changeoverfacilities 283 can be adapted to receive one or more bays 214 forcleaning or changing the components therein in preparation to performadditional runs of the same manufacturing processes or perform differentmanufacturing processes, identical to that which was described abovewith respect to the holding areas 24 of the system 10 depicted in FIGS.1-3. As depicted on the left-hand side of FIG. 5, the changeoverfacilities 283 can have a plurality of female components 273 adapted toreceive male components 271 to establish clean connect areas 249 betweenthe changeover facility 283 and the bays 214. As such, operatingpersonnel can access the bays 214 from the uncontrolled corridors 285through the clean connect areas 249 in a manner identical to that whichwas described above with reference to FIG. 4. Although not depicted, thechangeover facility 283 on the right-hand side of FIG. 5 can be equippedin a manner identical to the changeover facility 283 on the left-handside of FIG. 5.

Still referring to FIG. 5, the system 200 is further distinct from thesystems 10, 100 described above in that the core 212 includes twoseparate core components 212 a, 212 b connected together at an adjoiningwall 213. In essence, the two core components 212 a, 212 b areextensions of each other and operate in conjunction to provide utilitiesto the plurality of bays 214, as needed. In one embodiment, each corecomponent 212 a, 212 b is movable such that, if desired, the system 200could operate with a single core component, such as core component 212b, for example. Moreover, it is foreseeable that the system 200 could beequipped with additional core components (not shown) that could be movedinto position and connected to the existing core 212 to increase theoperating capacity of the entire system 200. These additional corecomponents could be attached to the end of core component 212 b, asillustrated by the arrow in FIG. 5.

In view of the foregoing, it should be appreciated that any of themethods of using the manufacturing systems 10, 100 described above withreference to FIG. 1 and FIG. 4 apply in the same manner to the system200 depicted in FIGS. 5 and 7, and therefore, the details thereof willnot be repeated.

Thus far, the present disclosure has described various systems 10, 100,200, 400 wherein movable bays 14, 114, 214, 414 are connected orconnectable to a core 12, 112, 212, 414 that supplies various utilitiesto the bays 14, 114, 214, 414. In each of the disclosed embodiments, thecore 12, 112, 212, 412 is located beside the bays 14, 114, 214, 414. Inan alternative embodiment, a system constructed in accordance with thepresent disclosure can be configured such that at least some of theutilities can be supplied to the bays 14, 114, 214, 414 from above toobtain various advantages, such as for example advantages associatedwith utilizing the force of gravity to deliver the utilities and/oradvantages of spatially separating the locations of utility couplingsand personnel access.

For example, FIG. 6 partially depicts an alternative embodiment of asystem 300 constructed in accordance with the present disclosure whereinone bay 314 of a plurality of bays is removably coupled to a core 312via a clean connect area 349 and removably coupled beneath an upperdocking collar 391. While FIG. 6 illustrates a single upper dockingcollar 391, the system 300 could include a plurality of docking collars391 disposed at a plurality of locations, respectively, on the core 312,at which any one of a plurality of bays 314 could be docked. Theplurality of docking collars 391 could be entirely independent, separateand disconnected from each other, connected, or contiguous. For example,although the description and claims may refer to a first docking collar,a second docking collar, etc., these two components may be portions of asingle contiguous docking collar. An interstitial maintenance space 392separates the upper docking collar 391 from the top of the bay 314 whenthe bay 314 is connected to the core 312. In the disclosed embodiment,the upper docking collar 391 extends outward from and is fixedly coupledto the core 312. Similar to the core 312, the upper docking collar 391is isolated from the bay 314 such that operating personnel cannot passbetween the bay 314 and the upper docking collar 391. In someembodiments, personnel can pass between the upper docking collar 391 andthe core 312.

As mentioned, the upper docking collar 391 supplies one or moreutilities to the bay 314. This can be facilitated by the incorporationof one or more conduits 393 extending downward from the upper dockingcollar 391 to the bay 314. That is, the collar 391 could include portsfor connecting to the conduits 393, which in some embodiments couldinclude lines, such as gamma irradiated disposable lines with valves forliquid transfer, for example. When the bay 314 is moved into positionbeneath the upper docking collar 391, as depicted, maintenance personnelcan access the interstitial maintenance space 392 to make theconnections between the upper docking collar 391 and bay 314 with theone or more conduits 393. It is foreseeable that the one or moreconduits may include electrical lines, data lines, air ducts, fluidlines, gas lines, etc.

In one embodiment, the one or more utilities supplied from the upperdocking collar 391 includes one or more of (a) clean air, (b) cleanwater, (c) electricity, (d) oxygen, (e) carbon dioxide, (f) anutritional media, (g) a dilution buffer, (h) a purification media, and(i) a local area network. Other embodiments could include otherutilities supplied from the upper docking collar 391. To supply cleanair to the bay 314, the upper docking collar 391 can be equipped withHVAC equipment. Positioning the HVAC equipment in the upper dockingcollar 391 above the bay 314 maximizes the amount of space available forexhausting heat and related gases through a roof 391 a of the upperdocking collar 391. Additionally, when the HVAC equipment is used toprovide cool air to the bay 314, positioning the HVAC equipment abovethe bay 314 facilitates the delivery of the cool air, which is heavierthan warm air, and therefore naturally travels downward under the forceof gravity. Moreover, storing clean water and the various liquid media,which is utilized during bio-manufacturing processes, in the upperdocking collar 391 allows for gravity feeding, which eliminates or atleast reduces the number of pumps required in the system. Reducing oreliminating the number of pumps required to operate the manufacturingfacility can advantageously reduce energy costs, maintenance costs, andheat generation, as well as increase the overall efficiency of thesystem.

In general, any of the methods of using the manufacturing systems 10,100, 200, 400 described above with reference to FIGS. 1, 4, 5, and 7apply in the same manner to the system 300 depicted in FIG. 6. However,the methods can also be modified to include various features related tothe clean connect area(s) 149 and/or upper docking collar(s) 391. Forexample, any method of manufacturing a plurality of products using thesystem 300 can further include connecting one or more movable bays 314to one or more corresponding upper docking collars 391 prior toperforming manufacturing processes in the movable bays 314. Moreover,any method of using the system 300 can further include delivering one ormore utilities under the force of gravity from the upper docking collars391 to the bays 314 during the respective manufacturing processes.

Moreover, in some embodiments, the force of gravity can be utilized todeliver one or more utilities to the bays without using the upperdocking collar 391 described with reference top FIG. 6. For example, asdescribed above with reference to FIGS. 4 and 7, in some embodiments,the utilities can be supplied to the bays 114, 414 from the core 112,412 via conduits 193 a, 193 b, 415. As discussed above, the conduits 193a, 193 b, 415 can be arranged to travel from the core 112, 412 above thebays 114, 414 such that they drop down and connect to the bays 114, 414.In such a configuration, at least some of the utilities delivered viathe conduits 193 a, 193 b, 415 could experience the force of gravityupon entering the bays 114, 414. Thus, it should be appreciated thatdelivering utilities to the bays 14, 114, 214, 314, 414 is not limitedto an embodiment that requires an upper docking collar 391, but rather,the upper docking collar 391 is merely one embodiment for accomplishingthis.

While various methods of manufacturing products have been describedherein as being distinct methods, it should be appreciated that anyaspect of the various methods, or the entire methods, may be combinedwith the other methods to construct a single method of manufacturingutilizing the system 10 disclosed herein.

While the bays of the various embodiments of the systems describedherein have been generally depicted as including static dimensionsdefining, some embodiments of the bays could be equipped with movablewalls, pop-out walls, or sections, for example, that would enable thesize of the workspace to be altered. So configured, the workspace sizecould be increased to accommodate large capacity manufacturingprocesses, and/or the external dimensions of the bays could be decreasedto facilitate the maneuverability of the bays during transport.

The foregoing embodiments serve only to illustrate the invention and arenot intended to limit the scope of the invention in any way. While theinventions have been described with an emphasis upon preferredembodiments, it will be obvious to those of ordinary skill in the artthat variations of the preferred arrangements and components may be usedwithin the manufacturing system and variations of the methods may beused. It is thus intended that the invention may be practiced otherwisethan as specifically described herein. Accordingly, this inventionincludes all modifications encompassed within the spirit and scope ofthe invention as defined by the following aspects, which represent anon-exhaustive listing of examples or embodiments of the invention, andthe appending claims.

Aspect 1: A manufacturing system comprising: a core adapted to supplytwo or more utilities to one or more manufacturing bays, wherein atleast two of the two or more utilities are selected from the groupconsisting of (a) clean air, (b) clean water, (c) electricity, (d)oxygen, and (e) carbon dioxide; a first movable manufacturing bayremovably coupled to or adapted to be removably coupled to the core andfor receiving the utilities; a first workspace defined by the firstmovable manufacturing bay and accommodating a first facility forperforming a first manufacturing process; a second movable manufacturingbay removably coupled to or adapted to be removably coupled to the coreand for receiving the utilities; and a second workspace defined by thesecond movable manufacturing bay, the second workspace isolated from thefirst workspace and accommodating a second facility for performing asecond manufacturing process in parallel with the first facilityperforming the first manufacturing process.

Aspect 2: A manufacturing system, comprising: a core for supplying oneor more utilities to one or more manufacturing bays; a first movablemanufacturing bay removably coupled to or adapted to be removablycoupled to the core for receiving the one or more utilities; a firstworkspace defined by the first movable manufacturing bay andaccommodating a first facility for performing a first manufacturingprocess; a first clean connect area adapted to be coupled to the firstmovable manufacturing bay and selectively isolated from the firstworkspace, the first clean connect area for performing at least one ofthe following functions when coupled to the first movable manufacturingbay: (a) controlling personnel flow to and from the first movablemanufacturing bay and (b) providing a clean area for connecting theutilities between the core and the first movable manufacturing bay; asecond movable manufacturing bay removably coupled to or adapted to beremovably coupled to the core for receiving the one or more utilities; asecond workspace defined by the second movable manufacturing bay, thesecond workspace isolated from the first workspace and accommodating asecond facility for performing a second manufacturing process inparallel with the first facility performing the first manufacturingprocess; and a second clean connect area adapted to be coupled to thesecond movable manufacturing bay and selectively isolated from thesecond workspace, the second clean connect area for performing at leastone of the following functions when coupled to the second movablemanufacturing bay: (a) controlling personnel flow to and from the secondmovable manufacturing bay and (b) providing a clean area for connectingthe utilities between the core and the second movable manufacturing bay.

Aspect 3: A manufacturing system comprising: a core supplying one ormore utilities to one or more manufacturing bays; a first movablemanufacturing bay removably coupled to or adapted to be removablycoupled to the core and receiving the utilities; a first workspacedefined by the first movable manufacturing bay and accommodating a firstfacility for performing a first manufacturing process; a second movablemanufacturing bay removably coupled to or adapted to be removablycoupled to the core and receiving the utilities; a second workspacedefined by the second movable manufacturing bay, the second workspaceisolated from the first workspace and accommodating a second facilityfor performing a second manufacturing process; and a surface (e.g.,wall, floor, counter and/or sink) or area, e.g., for aseptic processingdisposed within one of the first and second movable manufacturing bays,the surface having one, two, three or all organism counts selected fromthe group consisting of: (a) viable particulate air organism count of≤100 CFU/m³, (b) settling plate organism count of ≤50 CFU/4 hours, and(c) Replicate Organisms Detection and Counting (RODAC) plate organismcount of ≤25 CFU/plate.

Aspect 4: A manufacturing system, comprising: a core for supplying aplurality of utilities; a first movable manufacturing bay removablycoupled to the core for receiving the one or more utilities; a firstworkspace defined by the first movable manufacturing bay andaccommodating a first facility for performing a first manufacturingprocess; a first upper docking collar disposed above and removablycoupled to the first movable manufacturing bay when the first movablemanufacturing bay is connected to the core, the first upper dockingcollar for supplying at least one utility to the first manufacturing baythat is distinct from each of the plurality of utilities supplied by thecore; a second movable manufacturing bay removably coupled to the corefor receiving the one or more utilities; a second workspace defined bythe second movable manufacturing bay, the second workspace isolated fromthe first workspace and accommodating a second facility for performing asecond manufacturing process; and a second upper docking collar disposedabove and removably coupled to the second movable manufacturing bay whenthe second movable manufacturing bay is connected to the core, thesecond upper docking collar for supplying at least one utility to thesecond manufacturing bay that is distinct from each of the plurality ofutilities supplied by the core.

Aspect 5: The system of any one of the preceding aspects, wherein thefirst and second movable manufacturing bays are not connected to eachother.

Aspect 6: The system of any one of the preceding aspects, furthercomprising: a first clean connect area adapted to be disposed adjacentthe first movable manufacturing bay when the first movable manufacturingbay is connected to the core, the first clean connect area forperforming at least one of the following functions: (a) controllingaccess to and from the first movable manufacturing bay and (b) providinga clean area for connecting the utilities between the first movablemanufacturing bay and the core; and a second clean connect area adaptedto be disposed adjacent to the second movable manufacturing bay when thesecond movable manufacturing bay is connected to the core, the secondclean connect area for performing at least one of the followingfunctions: (a) controlling access to and from the second movablemanufacturing bay and (b) providing a clean area for connecting theutilities between the second movable manufacturing bay and the core.

Aspect 7: The system of any one of the preceding aspects, wherein atleast a portion of the first clean connect area is coupled to the coreand adapted to be removably coupled to the first movable manufacturingbay, and at least a portion of the second clean connect area is coupledto the core and adapted to be removably coupled to the second movablemanufacturing bay.

Aspect 8: The system of any one of the preceding aspects, wherein eachof the first and second clean connect areas comprises a bay entryportion and a bay exit portion isolated from each other.

Aspect 9: The system of any one of the preceding aspects, wherein thebay entry portion of each of the first and second clean connect areascomprises an exit point adapted to be connected to an entry point of thefirst and second movable manufacturing bays, respectively, such thatoperating personnel can pass from the first and second clean connectareas into the first and second movable manufacturing bays,respectively, when the first and second movable manufacturing bays areconnected to the core, and the bay exit portion of each of the first andsecond clean connect areas comprises an entry point adapted to beconnected to an exit point of the first and second movable manufacturingbays, respectively, such that operating personnel can pass from thefirst and second movable manufacturing bays into the first and secondclean connect areas, respectively, when the first and second movablemanufacturing bays are connected to the core.

Aspect 10: The system of any one of the preceding aspects, wherein thefirst and second movable manufacturing bays are sealed from the core,except for the supply of the two or more utilities, when the first andsecond movable bays are removably coupled to the core.

Aspect 11: The system of any one of the preceding aspects, wherein thecore is sealed from receiving incoming material from the first andsecond movable manufacturing bays.

Aspect 12: The system of any one of the preceding aspects, furthercomprising: first and second outlets associated with the core, each ofthe first and second outlets adapted to discharge at least one of theutilities; at least one first inlet associated with the first movablemanufacturing bay, the at least one first inlet adapted to be removablycoupled to the first outlet of the core; and at least one second inletassociated with second movable manufacturing bay, the at least onesecond inlet adapted to be removably coupled to the second outlet of thecore.

Aspect 13: The system of any one of the preceding aspects, wherein eachof the first and second outlets of the core comprises a plurality ofoutlets, each of the plurality of outlets adapted to supply a distinctutility of the two or more utilities, and each of the first and secondinlets of the first and second movable manufacturing bays, respectively,comprises a plurality of inlets adapted to be removably coupled to theplurality of outlets of the first and second outlets of the core,respectively, each of the plurality of first inlets for receiving adistinct utility from one of the plurality of first outlets and each ofthe plurality of second inlets for receiving a distinct utility from oneof the plurality of second outlets.

Aspect 14: The system of any one of the preceding aspects, wherein eachof the first and second facilities comprises a plurality of components,each of which is adapted to perform one or more steps of a chemical, abiological, or a pharmaceutical manufacturing process.

Aspect 15: The system of any one of the preceding aspects, wherein theplurality of components comprises at least one of a culturing component,a harvesting component, a purifying component, a biosafety cabinet, oneor more culture flasks, an incubator, a carbon dioxide incubator, a cellcounter, a cell viability measuring device, an osmolarity measuringdevice, a metabolite measuring device, a lactate dehydrogenase measuringdevice, a sealer, sterile connecting devices, a microscope, a waterbath, a peristaltic pump, a bioreactor, including single use ordisposable bioreactors, a wave bioreactor, a media batch tank, a bufferholding tank, an agitator, a sparger, a light house for plants, a tankfor growing algae/duckweed, a room for mushrooms, a pump, a piston pump,a diaphragm pump, a rotary lobe pump, a positive displacement pump, aflow control valve, a centrifuge component, a disk stack centrifuge, apressure regulator, a surge tank, a cell lysis component, a mechanicaldisruptor, a shredder and/or extractor and/or vacuum system forseparating proteins from plants, algae or mushrooms, a depth filtercomponent, a clarification filter, a holding tank, an ultrafiltrationcomponent, a diafiltration component, an ultrafiltration/diafiltrationsystem, a drain line, a heat removal component, a recirculation tankjacket, a heat exchanger, a laminar flow hood, a freezing system, one ormore cryovessels, one or more cold baths, one or more liquid nitrogensystems, one or more freeze/thaw components, a spray-dryer, afreeze-dryer, a buffer dilution skid, an ion exchange chromatographycolumn or membrane or skid or bed, an affinity chromatography column ormembrane or skid or bed, a hydrophobic interaction chromatography columnor membrane or skid or bed, a hydrophobic charge inductionchromatography column or membrane or skid or bed, a liquidchromatography column or membrane or skid or bed, a high pressure liquidchromatography column or membrane or skid or bed, a gas chromatographycolumn or membrane or skid or bed (for both separation of organicmolecules and for analysis), other separation technologies, a sizeexclusion chromatography column or membrane or skid or bed, a metalaffinity chromatography column or membrane or skid or bed, a protein Achromatography column or membrane or skid or bed, a hydroxyapatitecolumn or membrane or skid or bed, disposable purification systems,process control systems, a filter housing, an ultraviolet analyzer, aconductivity probe, a steam seal, a steam trap, a glasswasher, anautoclave, a sterilizing filter, one or more sterile containers, one ormore sterile vials, one or more sterile syringers, a lyophilizer, a fumehood (optionally connected to an outlet in the bay) and relatedequipment for chemical synthesis, an evaporator for removing solvents(optionally connected to an outlet in the bay), a crystallization systemfor purifying organics, one or more computer networks for individualbays and for the core facilities, one or more analytical devices forassaying products, electrophoresis equipment (eg, SDS-PAGE), a pH meter,a mass spectrometer, an IR spectrometer, a UV spectrophotometers (foranalysis or detection during processing), in-line analytics attached tofermentation and purification systems, disposable fermentation systemsfrom 20 L-5000 L or more using stir (e.g., Xcellerex) or movement (e.g.,GE Healthcare Wave), centrifugation equipment for either discontinuousor continuous separation, clean air hoods or containment systems forfilling, wiring for or wireless systems for monitoring or automatedprocesses, gas lines for clean air or specialty gases, water lines,pumps for fluid transfer, containers for product collection, freezer andcold room areas, non-aqueous solvent storage systems, control systemsand specialty software for automation and apparatus controls.

Aspect 16: The system of any one of the preceding aspects, wherein theplurality of components comprises at least one of a culturing component,a harvesting component, one or more culture flasks, an incubator, acarbon dioxide incubator, a cell counter, a bioreactor, a media batchtank, a cell lysis component, an autoclave, a sterilizing filter,electrophoresis equipment such as an SDS-PAGE.

Aspect 17: The system of any one of the preceding aspects, wherein theplurality of components comprises at least one of a purifying component,a biosafety cabinet, a sparger, a mechanical disruptor, anultrafiltration component, a diafiltration component, anultrafiltration/diafiltration system, a laminar flow hood, one or morecryovessels, an ion exchange chromatography column or membrane or skidor bed, an affinity chromatography column or membrane or skid or bed, ahydrophobic interaction chromatography column or membrane or skid orbed, a hydrophobic charge induction chromatography column or membrane orskid or bed, a size exclusion chromatography column or membrane or skidor bed, a metal affinity chromatography column or membrane or skid orbed, a protein A chromatography column or membrane or skid or bed, ahydroxyapatite column or membrane or skid or bed, a liquidchromatography column or membrane or skid or bed, a high pressure liquidchromatography column or membrane or skid or bed, a gas chromatographycolumn or membrane or skid or bed, a lyophilizer, one or more extractorsystems, one or more evaporators each with an outlet in the bay,crystallization systems for purifying organics, one or more in-lineanalytics attached to fermentation and purification systems, one or moredisposable fermentation systems.

Aspect 18: The system of any one of the preceding aspects, wherein theculturing component comprises a bioreactor.

Aspect 19: The system of any one of the preceding aspects, wherein thepurifying component comprises a chromatography system.

Aspect 20: The system of any one of the preceding aspects, wherein thefirst movable manufacturing bay comprises a first control system forcontrolling the first manufacturing process, and the second movablemanufacturing bay comprises a second control system for controlling thesecond manufacturing process independent of the first manufacturingprocess.

Aspect 21: The system of any one of the preceding aspects, wherein eachof the first and second movable manufacturing bays comprises a drain fordischarging waste generated during the first and second manufacturingprocesses, respectively.

Aspect 22: The system of any one of the preceding aspects, wherein atleast one of the bay entry portion and the bay exit portion of each ofthe first and second clean connect areas contains no more thanapproximately 10,000 particles 0.5 microns and larger per cubic foot ofair.

Aspect 23: The system of any one of the preceding aspects, wherein eachof the first and second workspaces defined by the first and secondmovable manufacturing bays, respectively, contains a number of particlesthat are 0.5 microns and larger per cubic foot of air, the number beingin the range of approximately 1 to approximately 100,000.

Aspect 24: The system of any one of the preceding aspects, wherein thenumber of particles is approximately 10,000.

Aspect 25: The system of any one of the preceding aspects, furthercomprising: a first upper docking collar adapted to be disposed abovethe first movable manufacturing bay and removably connected to the firstmovable manufacturing bay when the first movable manufacturing bay isconnected to the core, the first upper docking collar containing atleast one utility for being supplied to the first workspace whileperforming the first manufacturing process; and a second upper dockingcollar adapted to be disposed above the second movable manufacturing bayand removably connected to the second movable manufacturing bay when thesecond movable manufacturing bay is connected to the core, the secondupper docking collar containing at least one utility for being suppliedto the second workspace while performing the second manufacturingprocess.

Aspect 26: The system of any one of the preceding aspects, wherein thefirst and second upper docking collars are fixedly coupled to the core.

Aspect 27: The system of any one of the preceding aspects, wherein theat least one utility contained within the first and second upper dockingcollars is selected from the group consisting of: (a) clean air, (b)clean water, (c) electricity, (d) oxygen, (e) carbon dioxide, (f) anutritional media, (g) a dilution buffer, (h) a purification media, and(i) a local area network.

Aspect 28: The system of any one of the preceding aspects, wherein atleast one of the first movable manufacturing bay and the second movablemanufacturing bay comprises a hood for aseptic processing, the hoodhaving one, two, three or all organism counts selected from the groupconsisting of: (a) viable particulate air organism count of <1 CFU/m³,(b) settling plate organism count of <1 CFU/4 hours, (c) ReplicateOrganisms Detection and Counting (RODAC) plate organism count of <1CFU/plate, and (d) touch plate organism count of <1 CFU/plate.

Aspect 29: The system of any one of the preceding aspects, wherein atleast one of the first movable manufacturing bay and the second movablemanufacturing bay comprises a surface (e.g., wall, floor, counter and/orsink) or area, e.g., for aseptic processing, the surface having one,two, three or all organism counts selected from the group consisting of:(a) viable particulate air organism count of ≤10 CFU/m³, (b) settlingplate organism count of ≤5 CFU/4 hours, (c) Replicate OrganismsDetection and Counting (RODAC) plate organism count of ≤5 CFU/plate, and(d) touch plate organism count of ≤5 CFU/plate.

Aspect 30: The system of any one of the preceding aspects, wherein atleast one of the first movable manufacturing bay and the second movablemanufacturing bay comprises a surface (e.g., wall, floor, counter and/orsink) or area, e.g., for fermentation and/or purification processes, thesurface having one, two, three or all organism counts selected from thegroup consisting of: (a) viable particulate air organism count of ≤100CFU/m³, (b) settling plate organism count of ≤50 CFU/4 hours, and (c)Replicate Organisms Detection and Counting (RODAC) plate organism countof ≤25 CFU/plate.

Aspect 31: The system of any one of the preceding aspects, furthercomprising one of a transfer panel and a controlled corridor disposedbetween the first and second movable manufacturing bays for facilitatingthe transfer of product therebetween.

Aspect 32: The system of any one of the preceding aspects, furthercomprising a housing containing at least one of the core, the firstmovable manufacturing bay, and the second movable manufacturing bay.

Aspect 33: The system of any one of the preceding aspects, furthercomprising a housing containing the core, the first movablemanufacturing bay, and the second movable manufacturing bay.

Aspect 34: The system of any one of the preceding aspects, wherein thehousing comprises a holding area disposed away from the core where eachof the first and second movable manufacturing bays can be positioned toundergo a cleaning operation, whereby the workspaces of the first andsecond movable manufacturing bays are cleaned, or a change-overoperation, whereby the facilities of the first and second movablemanufacturing bays are altered.

Aspect 35: The system of any one of the preceding aspects, wherein thecore, the first movable manufacturing bay, and the second movablemanufacturing bay are arranged in a hub and spoke configuration with thefirst and second movable manufacturing bays circumferentially spacedaround the core.

Aspect 36: A method of manufacturing a plurality of products,comprising: removably connecting a first movable bay to a core;performing a first manufacturing process with a first configuration ofcomponents disposed within the first movable bay to manufacture a firstproduct; disconnecting the first movable bay from the core; establishinga second configuration of components within the first movable bay;re-connecting the first movable bay to the core; and performing a secondmanufacturing process with the second configuration of components tomanufacture a second product, the second manufacturing process beingdistinct from the first manufacturing process.

Aspect 37: A method of manufacturing a plurality of products,comprising: removably connecting a first movable bay to a first positionof a core, the first position selected from a plurality of positions;performing a first manufacturing process with a configuration ofcomponents disposed within the first movable bay to manufacture a firstproduct; disconnecting the first movable bay from the first position ofthe core; removably connecting a second movable bay to the firstposition of the core; and performing a second manufacturing process witha configuration of components disposed within the second movable bay tomanufacture a second product.

Aspect 38: A method of manufacturing, comprising: selecting a first bayfrom a plurality of available bays; removably connecting the first bayto the core; selecting a second bay from the plurality of availablebays; removably connecting the second bay to the core; performing afirst manufacturing process with a first set of components disposedwithin the first bay to manufacture a first product; and performing asecond manufacturing process in parallel with the first manufacturingprocess with a second set of components disposed within the second bayto manufacture a second product.

Aspect 39: A method of manufacturing, comprising: selecting a first bayfrom a plurality of available bays; moving the first bay to a positionoutside of a core; removably connecting the first bay to the core;selecting a second bay from the plurality of available bays; moving thesecond bay to a position outside of the core; removably connecting thesecond bay to the core; performing a first manufacturing process for afirst product with a first set of components disposed within the firstbay to bring the first product to a first stage of manufacture; andperforming a second manufacturing process for the first product with asecond set of components disposed within the second bay to bring thefirst product to a second stage of manufacture.

Aspect 40: The method of any one of the preceding aspects, furthercomprising supplying at least one utility to the first movable bay, orto the first and second movable bays, from the core when the firstmovable bay is, or the first and second movable bays are, connected tothe core, the at least one utility comprising at least one of (a) cleanair, (b) clean water, (c) electricity, (d) oxygen, or (e) carbondioxide.

Aspect 41: The method of any one of the preceding aspects, furthercomprising supplying two or more utilities to the first movable bay, orto the first and second movable bays, from the core, at least two of thetwo or more utilities selected from the group consisting of (a) cleanair, (b) clean water, (c) electricity, (d) oxygen, and (e) carbondioxide.

Aspect 42: The method of any one of the preceding aspects, furthercomprising supplying three or more utilities to the first movable bay,or to the first and second movable bays, from the core, at least threeof the three or more utilities selected from the group consisting of (a)clean air, (b) clean water, (c) electricity, (d) oxygen, and (e) carbondioxide.

Aspect 43: The method of any one of the preceding aspects, whereinremovably connecting the first movable bay to the core comprisesconnecting at least one inlet of the first movable bay to at least oneoutlet of the core, wherein the at least one outlet of the core suppliesat least one utility, disconnecting the first movable bay from the corecomprises disconnecting the at least one inlet of the first movable bayfrom the at least one outlet of the core, and re-connecting the firstmovable bay to the core comprises re-connecting the at least one inletof the first movable bay to the at least one outlet of the core.

Aspect 44: The method of any one of the preceding aspects, whereinremovably connecting the first and second movable bays to the corecomprises connecting at least one inlet of the first and second movablebays to at least one outlet of the core, wherein the at least one outletof the core supplies at least one utility.

Aspect 45: The method of any one of the preceding aspects, whereinconnecting the at least one inlet of the first and second movable baysto the at least one outlet of the core comprises connecting a pluralityof outlets of the core to a plurality of inlets of the first and secondmovable bays, wherein each of the plurality of outlets supplies adistinct utility.

Aspect 46: The method of any one of the preceding aspects, furthercomprising: removably connecting the first movable bay to a first cleanconnect area prior to performing the first manufacturing process, thefirst clean connect area for performing at least one of the followingfunctions (a) controlling personnel flow to and from the first movablebay and (b) providing a clean area for connecting the utilities betweenthe core and the first movable bay; disconnecting the first movable bayfrom the first clean connect area prior to removably connecting thesecond movable bay to the first position of the core; and removablyconnecting the second movable bay to the first clean connect area priorto performing the second manufacturing process.

Aspect 47: The method of any one of the preceding aspects, whereinremovably connecting the first and second movable bays to the firstclean connect area comprises connecting an entry point of each of thefirst and second movable bays to an exit point of the first cleanconnect area and connecting an exit point of each of the first andsecond movable bays to an entry point of the first clean connect area;and disconnecting the first movable bay from the first clean connectarea comprises disconnecting the entry point of the first movable bayfrom the exit point of the first clean connect area and disconnectingthe exit point of the first movable bay from the entry point of thefirst clean connect area.

Aspect 48: The method of any one of the preceding aspects, furthercomprising: removably connecting the first movable bay to a first upperdocking collar located above the first movable bay when the firstmovable bay is connected to the first position of the core prior toperforming the first manufacturing process, the first upper dockingcollar adapted to deliver the one or more utilities to the first movablebay during the first manufacturing process; and removably connecting thesecond movable bay to the first upper docking collar located above thesecond movable bay when the second movable bay is connected to the firstposition of the core prior to performing the second manufacturingprocess, the first upper docking collar adapted to deliver the one ormore utilities to the second movable bay during the second manufacturingprocess.

Aspect 49: The method of any one of the preceding aspects, furthercomprising delivering one or more utilities from the first upper dockingcollar to at least one of the first and second movable bays during atleast one of the first and second manufacturing processes.

Aspect 50: The method of any one of the preceding aspects, furthercomprising: moving the first movable bay to a holding area disposed awayfrom the core after disconnecting the first movable bay from the core,and (i) cleaning the first movable bay or (ii) establishing a differentconfiguration of components within the first movable bay.

Aspect 51: The method of any one of the preceding aspects, furthercomprising: moving the first bay adjacent to the core after selectingthe first bay; and moving the second bay adjacent to the core afterselecting the second bay.

Aspect 52: The method of any one of the preceding aspects, furthercomprising: selecting a third bay from the plurality of available bays;removably connecting the third bay to the core; performing a thirdmanufacturing process in parallel with at least one of the first andsecond manufacturing processes with a third set of components disposedwithin the third bay to manufacture a third product.

Aspect 53: The method of any one of the preceding aspects, whereinremovably connecting the first bay to the core comprises connecting atleast one first inlet of the first bay to at least one first outlet ofthe core; and removably connecting the second bay to the core comprisesconnecting at least one second inlet of the second bay to at least onesecond outlet of the core.

Aspect 54: The method of any one of the preceding aspects, furthercomprising: removably connecting the first bay to a first clean connectarea prior to performing the first manufacturing process, the firstclean connect area for performing at least one of the followingfunctions (a) controlling personnel flow to and from the first bay and(b) providing a clean area for connecting the utilities between the coreand the first bay; removably connecting the second movable bay to asecond clean connect area prior to performing the second manufacturingprocess, the second clean connect area for performing at least one ofthe following functions (a) controlling personnel flow to and from thesecond bay and (b) providing a clean area for connecting the utilitiesbetween the core and the second bay.

Aspect 55: The method of any one of the preceding aspects, whereinremovably connecting the first bay to the first clean connect areacomprises connecting an entry point of the first bay to an exit point ofthe first clean connect area and connecting an exit point of the firstbay to an entry point of the first clean connect area; and removablyconnecting the second bay to the second clean connect area comprisesconnecting an entry point of the second bay to an exit point of thesecond clean connect area and connecting an exit point of the second bayto an entry point of the second clean connect area.

Aspect 56: The method of any one of the preceding aspects, furthercomprising: removably connecting the first bay to a first upper dockingcollar located above the first bay when the first bay is connected tothe core prior to performing the first manufacturing process, the firstupper docking collar adapted to deliver the one or more utilities to thefirst bay during the first manufacturing process; and removablyconnecting the second bay to a second upper docking collar located abovethe second bay when the second bay is connected to the core prior toperforming the second manufacturing process, the second upper dockingcollar adapted to deliver the one or more utilities to the second bayduring the second manufacturing process.

Aspect 57: The method of any one of the preceding aspects, furthercomprising delivering one or more utilities from the first upper dockingcollar to the first bay during the first manufacturing process,delivering one or more utilities from the second upper docking collar tothe second bay during the second manufacturing process.

Aspect 58: The method of any one of the preceding aspects, furthercomprising: controlling the first manufacturing process with a firstcontrol system associated with the first bay; and controlling the secondmanufacturing process with a second control system associated with thesecond bay, the first and second control systems being distinct controlsystems.

Aspect 59: The method of any one of the preceding aspects, whereincontrolling the second manufacturing process comprises controlling thesecond manufacturing process independently of the first manufacturingprocess.

Aspect 60: The method of any one of the preceding aspects, furthercomprising: disconnecting the first bay from the core after performingthe first manufacturing process; moving the first bay to a holding areadisposed away from the core; performing at least one of the followingoperations: (a) cleaning the first set of components to define a thirdset of components, (b) reconfiguring the first set of components todefine a third set of components, and (c) replacing at least some of thefirst set of components with a third set of components; removablyre-connecting the first bay to the core; and performing a thirdmanufacturing process with the third set of components in the first bayin parallel with the second set of components in the second bayperforming the second manufacturing process.

Aspect 61: The method of any one of the preceding aspects, furthercomprising moving the first bay to a position adjacent to the core priorto removably re-connecting the first bay to the core.

Aspect 62: The method of any one of the preceding aspects, furthercomprising moving the first product at the first stage of manufacturefrom the first bay to the second bay.

Aspect 63: The method of any one of the preceding aspects, whereinmoving the first product from the first bay to the second bay comprisestransferring the first product from the first bay to the second bay.

Aspect 64: The method of any one of the preceding aspects, whereintransferring the first product from the first bay to the second baycomprises one or more of the following actions: (a) transferring thefirst product from the first bay to the second through a conduit, aline, a tube, or other connecting means, and (b) transporting the firstproduct from the first bay to the second bay in a container or vessel.

Aspect 65: The method of any one of the preceding aspects, whereinpumping the first product comprises pumping the first product through atleast one transfer panel comprising a conduit that extends from thefirst bay to the second bay.

Aspect 66: The method of any one of the preceding aspects, whereincarrying the first product from the first bay to the second baycomprises moving the first product through a controlled corridordisposed between the first bay and the second bay.

Aspect 66: The method of any one of the preceding aspects, furthercomprising: selecting a third bay from the plurality of available bays;moving the third bay to a position outside of the core; removablyconnecting the third bay to the core; performing a third manufacturingprocess on the first product with a third set of components disposedwithin the third bay to bring the first product to a third stage ofmanufacture.

Aspect 67: The method of any one of the preceding aspects, furthercomprising: removably connecting the first movable bay to a first cleanconnect area prior to performing the first manufacturing process, theclean connect area for performing at least one of the followingfunctions (a) controlling personnel flow to and from the first movablebay and (b) providing a clean are for connecting the utilities betweenthe first movable bay and the core; disconnecting the first movable bayfrom the first clean connect area prior to establishing the secondconfiguration of components within the first movable bay; andre-connecting the first movable bay to the first clean connect areaprior to performing the second manufacturing process.

Aspect 68: The method of any one of the preceding aspects, whereinconnecting the at least one inlet of the first movable bay to the atleast one outlet of the core comprises connecting a plurality of outletsof the core to a plurality of inlets of the first movable bay, whereineach of the plurality of outlets supplies a distinct utility,disconnecting the at least one inlet of the first movable bay from theat least one outlet of the core comprises disconnecting the plurality ofinlets from the plurality of outlets, and re-connecting the at least oneinlet of the first movable bay to the at least one outlet of the corecomprises re-connecting the plurality of inlets to the plurality ofoutlets.

Aspect 69: The method of any one of the preceding aspects, whereinremovably connecting and re-connecting the first movable bay to thefirst clean connect area comprises connecting an entry point of thefirst movable bay to an exit point of the first clean connect area andconnecting an exit point of the first movable bay to an entry point ofthe first clean connect area; and disconnecting the first movable bayfrom the first clean connect area comprises disconnecting the entrypoint of the first movable bay from the exit point of the first cleanconnect area and disconnecting the exit point of the first movable bayfrom the entry point of the first clean connect area.

Aspect 70: The method of any one of the preceding aspects, furthercomprising: removably connecting the first movable bay to a first upperdocking collar located above the first movable bay prior to performingthe first manufacturing process, the first upper docking collar adaptedto deliver the one or more utilities to the first movable bay during atleast one of the first and second manufacturing processes; disconnectingthe first movable bay from the first upper docking collar prior toestablishing the second configuration of components within the firstmovable bay; and re-connecting the first movable bay to the first upperdocking collar prior to performing the second manufacturing process.

Aspect 71: The method of any one of the preceding aspects, furthercomprising delivering one or more utilities from the first upper dockingcollar to the first movable bay during at least one of the first andsecond manufacturing processes.

Aspect 72: The method of any one of the preceding aspects, wherein theat least one utility is selected from the group consisting of (a) cleanair, (b) clean water, (c) a nutritional media, (d) a dilution buffer,and (e) a purification media.

Aspect 73: The method of any one of the preceding aspects, furthercomprising maintaining a hood for aseptic processing within the firstmovable manufacturing bay to have one, two, three or all organism countsselected from the group consisting of: (a) viable particulate airorganism count of <1 CFU/m³, (b) settling plate organism count of <1CFU/4 hours, (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of <1 CFU/plate, and (d) touch plate organism countof <1 CFU/plate.

Aspect 74: The method of any one of the preceding aspects, furthercomprising maintaining a surface (e.g., wall, floor, counter and/orsink) or area, e.g., for aseptic processing, within the first movablemanufacturing bay to have one, two, three or all organism countsselected from the group consisting of: (a) viable particulate airorganism count of ≤10 CFU/m³, (b) settling plate organism count of ≤5CFU/4 hours, (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of ≤5 CFU/plate, and (d) touch plate organism countof ≤5 CFU/plate.

Aspect 75: The method of any one of the preceding aspects, furthercomprising maintaining a surface (e.g., wall, floor, counter and/orsink) or area, e.g., for aseptic processing, within the first movablemanufacturing bay to have one, two, three or all organism countsselected from the group consisting of: (a) viable particulate airorganism count of ≤100 CFU/m³, (b) settling plate organism count of ≤50CFU/4 hours, and (c) Replicate Organisms Detection and Counting (RODAC)plate organism count of ≤25 CFU/plate.

Aspect 76: The method of any one of the preceding aspects, furthercomprising: moving the first movable bay to a holding area disposed awayfrom the core after disconnecting the first movable bay from the coreand prior to establishing a second configuration of components withinthe first movable bay.

Aspect 77: The method of any one of the preceding aspects, furthercomprising cleaning the first movable bay prior to establishing thesecond configuration of components in the first movable bay.

Aspect 78: The method of any one of the preceding aspects, whereinperforming each of the first and second manufacturing processescomprises performing one of a chemical, a biological, and apharmaceutical manufacturing process.

Aspect 79: The method of any one of the preceding aspects, wherein thechemical, biological, or pharmaceutical manufacturing process isselected from the group consisting of cell inoculum preparation;culturing or fermentation of mammalian cells such as Chinese hamsterovary (CHO) cells, mouse myeloma cell lines, human embryonic kidney,human retinal cells, NS0, HEK293, PER.C6, or cells suitable forreplicating viruses, such as African green monkey VERO, MDCK (caninekidney cells), CEF (chicken embryonic fibroblasts), 2BS, Mark145, ST1,DF-1, CIK, EPC; incubation of chicken eggs for vaccine production;culturing or fermentation of bacterial or prokaryotic cells, includingbut not limited to gram-negative or gram-positive organisms,Enterobacteriaceae such as E. coli, e.g. E. coli K12 strain, E. coliX1776 strain, E. coli W3110 strain, and E. coli K5, Enterobacter,Pseudomonas such as P. fluorescens and P. aeruginosa, Erwinia,Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia,e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B.subtilis and B. licheniformis, or Streptomyces; culturing fermentationof yeast or fungal cells, including but not limited to Saccharomyces,e.g. S. cerevisiae, Schizosaccharomyces pombe, Kluyveromyces, Pichia,e.g. P. pastoris, Candida, Trichoderma, Neurospora, e.g. N. crassa,Schwannomyces, filamentous fungi such as, e.g., Neurospora, Penicillium,Tolypocladium, neosporidia, Aspergillus, e.g. A. nidulans and A. niger,Hansenula, Kloeckera, Torulopsis, or Rhodotorula; culturing insectcells, e.g. baculoviral systems, Sf9 cells; growing plant cells,including but not limited to algae, tobacco, algae, duckweed, ormushrooms; inoculating cells or chicken eggs with virus; harvestingcells or virus or culture medium; inactivated vaccine production,including but not limited to heat killed pneumococcal orformalin-treated viruses, live vaccine production, including replicationof influenza, or other viruses for vaccines, e.g. measles, mumps,rubella, varicella, polio, rabies, H5N1 virus; viral vector production,including but not limited to adenovirus, AAV, alphavirus, poxvirus,retrovirus, picornavirus, paramyxovirus, rhabdovirus; counting cells,cell viability measurement, osmolarity measurement, metabolitemeasurement, lactate dehydrogenase measurement; lysing cells;centrifugation processes; filtration processes; freezing processes,including freezing of purified bulk product; thawing processes;purification processes, including but not limited to ion exchangechromatography, affinity chromatography, hydrophobic interactionchromatography, hydrophobic charge induction chromatography, sizeexclusion chromatography, metal affinity chromatography, protein Achromatography, hydroxyapatite separation, multicolumn countercurrentsolvent gradient purification process, buffer dilution processes,formulation and/or filing processes, including but not limited to addingexcipients, sterile filtration, filling processes, freeze-drying,spray-drying, pegylation, sealing, labeling, process control, liquidnitrogen storage; peptide synthesis and/or purification processes; siRNAsynthesis and/or purification processes; synthesis and/or purificationof small organic molecules.

What is claimed is:
 1. A unitary structure adapted to be disposed withina housing, comprising: at least one controlled air, sealable,sterilizable cleanroom having an entry point and an exit point; acleanroom entry portion coupled to and selectively isolated from thecleanroom, the cleanroom entry portion for controlling personnel flow tothe cleanroom via the entry point; a cleanroom exit portion coupled toand selectively isolated from the cleanroom and separated from thecleanroom entry portion, the cleanroom exit portion for controllingpersonnel flow from the cleanroom via the exit point; means forpermitting movement of the cleanroom within the housing; and amechanical system room that, when connected to the cleanroom, is fixedrelative to the cleanroom, the mechanical system room comprising: atleast two air handling units that provide air to the cleanroom with atleast Class 100,000 air purity, the air handling units connected to thecleanroom via one or more supply outlets, wherein a pressuredifferential is formed between the cleanroom and the exterior of thestructure; and at least two power supplies that provide power toelectrical outlets in the cleanroom, wherein the at least two powersupplies are connectable to one or more external electrical powersources, wherein when one of the at least two air handling units breaksdown, the other of the at least two air handling units provides air tothe cleanroom without interruption, and wherein when one of the at leasttwo power supplies breaks down, the other of the at least two powersupplies provides power to the electrical outlets in the cleanroomwithout interruption.
 2. The structure of claim 1, further comprising acontrol system for controlling a manufacturing process performed in thecleanroom, wherein the control system comprises one or more sensors. 3.The structure of claim 1, further comprising one or more outlets adaptedto supply the clean room with at least one of sterile water, non-sterilewater, purified water, steam, wastewater, and gas.
 4. The structure ofclaim 3, further comprising one or more duplicate systems for supplyingthe cleanroom with at least one of sterile water, non-sterile water,purified water, steam, wastewater, and gas to ensure no loss ofproductivity.
 5. The structure of claim 1, further comprising equipmentfixed to the structure, the equipment comprising at least one of acentrifuge, a hood, a tank, a chromatography column, a bioreactor, arefrigerator, a freezer, an incubator, a biosafety cabinet, a vacuumsystem, and a freeze drier.
 6. The structure of claim 1, wherein the atleast one controlled air, sealable, sterilizable cleanroom comprisesfirst and second controlled air, sealable, sterilizable cleanrooms, thefirst cleanroom being serviceable without interrupting one or moremanufacturing processes being performed in the second cleanroom.
 7. Thestructure of claim 1, wherein a first controlled air, sealable,sterilizable cleanroom can be swapped out for a second controlled air,sealable, sterilizable cleanroom.
 8. The structure of claim 1, whereinthe structure comprises at least one of one or more reinforced floors orone or more suspension systems.
 9. The structure of claim 1, wherein theone or more supply outlets are adapted to vary the internal pressure inthe cleanroom, thereby varying the pressure differential between thecleanroom and the exterior of the structure.
 10. The structure of claim9, wherein the internal pressure can be varied to be greater than, lessthan, or equal to a pressure of the exterior of the structure.
 11. Thestructure of claim 1, wherein the cleanroom is provided with at leastClass 10,000, 1,000, 100 or 10 air purity.
 12. The structure of claim 1,wherein the cleanroom comprises bioprocess equipment, the bioprocessequipment comprising at least one of culture media, water, solvents, anddisposables.
 13. The structure of claim 1, wherein the cleanroomcomprises at least one of a work table, a work surface, cabinetry,surveillance equipment, bags, office items, and chairs.
 14. Thestructure of claim 1, wherein the one or more supply outlets aresealable.
 15. The structure of claim 1, wherein the cleanroom furthercomprises one or more sealable corridors to transfer materials to andfrom the cleanroom.
 16. The structure of claim 1, wherein the structureis adapted for transport via land, sea or air.
 17. The structure ofclaim 1, wherein the cleanroom is isolated from other portions of thestructure such that the structure complies with GMP manufacturingguidelines.
 18. The structure of claim 1, wherein the structure isportable.
 19. The structure of claim 1, further comprising a cleanconnect area disposed between the cleanroom and the mechanical systemroom.
 20. The structure of claim 19, wherein the clean connect areafacilitates movement between the cleanroom and the mechanical systemroom.
 21. The structure of claim 19, wherein the clean connect areaconnects the cleanroom and the mechanical system room.
 22. The structureof claim 1, wherein the mechanical system room is removably connected tothe cleanroom.
 23. The structure of claim 1, further comprising avertical wall separating the cleanroom and the mechanical system room.24. The structure of claim 1, wherein the means for permitting movementof the cleanroom is arranged under the cleanroom.
 25. The structure ofclaim 1, wherein the means for permitting movement of the cleanroomcomprises rails, wheels, or tracks.
 26. The structure of claim 1,wherein the means for permitting movement of the cleanroom comprises anair cushion arranged under the cleanroom.
 27. A facility adapted to bedisposed within a housing, comprising: at least one controlled air,sealable, sterilizable cleanroom having an entry point and an exitpoint; a cleanroom entry portion coupled to and selectively isolatedfrom the cleanroom, the cleanroom entry portion for controllingpersonnel flow to the cleanroom via the entry point; a cleanroom exitportion coupled to and selectively isolated from the cleanroom andseparated from the cleanroom entry portion, the cleanroom exit portionfor controlling personnel flow from the cleanroom via the exit point;means for permitting movement of the cleanroom within the housing; asupport room adjacent the cleanroom; a vertical wall separating thecleanroom and the support room; at least two air handling units in thesupport room that provide air to the cleanroom with at least Class100,000 air purity, the air handling units connected to the cleanroomvia one or more supply outlets, wherein a pressure differential isformed between the cleanroom and the exterior of the structure; and atleast two power supplies that provide power to electrical outlets in thecleanroom, wherein the at least two power supplies are connectable toone or more external power sources, wherein when one of the at least twoair handling units breaks down, the other of the at least two airhandling units provides air to the cleanroom without interruption,wherein when one of the at least two power supplies breaks down, theother of the at least two power supplies provides power to theelectrical outlets in the cleanroom without interruption.
 28. Thefacility of claim 27, wherein the means for permitting movement of thecleanroom is arranged under the cleanroom.
 29. The facility of claim 27,wherein the means for permitting movement of the cleanroom comprisesrails, wheels, or tracks.
 30. The facility of claim 27, wherein themeans for permitting movement of the cleanroom comprises an air cushionarranged under the cleanroom.
 31. The facility of claim 27, wherein themeans for permitting movement of the cleanroom comprises means forpermitting movement of the cleanroom relative to the support room.
 32. Aunit adapted to be disposed within a housing, comprising: at least onecontrolled air, sealable, sterilizable cleanroom having an entry pointand an exit point; a cleanroom entry portion coupled to and selectivelyisolated from the cleanroom, the cleanroom entry portion for controllingpersonnel flow to the cleanroom via the entry point; a cleanroom exitportion coupled to and selectively isolated from the cleanroom andseparated from the cleanroom entry portion, the cleanroom exit portionfor controlling personnel flow from the cleanroom via the exit point;means for permitting movement of the cleanroom within the housing; amechanical system room that, when connected to the cleanroom, is fixedrelative to the cleanroom; and a vertical wall separating the cleanroomand the mechanical system room, wherein the mechanical system roomcomprises two or more redundant systems, the redundant systemscomprising: at least two air handling units that provide air to thecleanroom with at least Class 100,000 air purity, the air handling unitsconnected to the clean room via one or more supply outlets, wherein apressure differential is formed between the cleanroom and the exteriorof the unit; and at least two power supplies that provide power toelectrical outlets in the cleanroom, wherein the at least two powersupplies are connectable to one or more external power sources, whereinwhen one of the at least two air handling units breaks down, the otherof the at least two air handling units provides air to the cleanroomwithout interruption, and wherein when one of the at least two powersupplies breaks down, the other of the at least two power suppliesprovides power to the electrical outlets in the cleanroom withoutinterruption.
 33. The unit of claim 32, wherein the means for permittingmovement of the cleanroom is arranged under the cleanroom.
 34. The unitof claim 32, wherein the means for permitting movement of the cleanroomcomprises rails, wheels, or tracks.
 35. The unit of claim 32, whereinthe means for permitting movement of the cleanroom comprises an aircushion arranged under the cleanroom.
 36. A method of making a unitaryunit adapted to be disposed within a housing, the method comprising:building at least one controlled air, sealable, sterilizable cleanroom,the cleanroom having an entry point and an exit point, and the cleanroomcomprising means for permitting movement of the cleanroom within thehousing; connecting a cleanroom entry portion to the cleanroom, thecleanroom entry portion selectively isolated from the cleanroom, thecleanroom entry portion for controlling personnel flow to the cleanroomvia the entry point; connecting a cleanroom exit portion to thecleanroom, the cleanroom exit portion selectively isolated from thecleanroom and separated from the cleanroom entry portion, the cleanroomexit portion for controlling personnel flow from the cleanroom via theexit point; and connecting a mechanical system room to the cleanroom,wherein when the mechanical system room is connected to the cleanroom,the mechanical system room is fixed relative to the mechanical systemroom, the mechanical system room comprising: at least two air handlingunits that provide air to the cleanroom with at least Class 100,000 airpurity, the air handling units connected to the cleanroom via one ormore supply outlets, wherein a pressure differential is formed betweenthe cleanroom and the exterior of the unit; and at least two powersupplies that provide power to electrical outlets in the cleanroom fromtwo sources, wherein the at least two power supplies are connectable toone or more external electrical power sources, wherein when one of theat least two air handling units breaks down, the other of the at leasttwo air handling units provides air to the cleanroom withoutinterruption, and wherein when one of the at least two power suppliesbreaks down, the other of the at least two power supplies provides powerto the electrical outlets in the cleanroom without interruption.